Onset Patterns Research Articles

Clinical ocular prediction model of postoperative ametropic amblyopia in patients with congenital ectopia lentis

IntroductionDespite prompt and appropriate surgical management, a considerable proportion of patients with congenital ectopia lentis (CEL) suffer from postoperative ametropic amblyopia. To predict and identify at-risk patients early, and ensure timely amblyopia treatment, we conducted a thorough investigation into the onset and progression patterns of postoperative amblyopia in patients with CEL. Moreover, an ocular prediction model was constructed for amblyopia.MethodsIn this prospective cohort study, amblyopia analysis was conducted to reveal the prevalence of postoperative amblyopia at different time points of follow-up. Comparative analysis and logistic regression analysis were performed for the development of an amblyopia prediction model. Receiver Operating Characteristic (ROC) analysis, calibration plots, and decision curve analysis (DCA) were used to evaluate the performance of the model. A nomogram was created to determine the probability of postoperative amblyopia. Amblyopia was diagnosed according to the most recent edition of the Amblyopia Preferred Practice Pattern.ResultsA total of 889 eyes from 677 patients operated for CEL were enrolled in this study. In the pediatric cohort, the prevalence of amblyopia showed a decreasing trend with follow-up time from 1 month to 3.5 years. A prediction model based on preoperative best-corrected visual acuity (BCVA) and cardiac phenotype was established to predict postoperative amblyopia. For effective individual prediction, a nomogram was created. With great calibration, discrimination, and clinical usefulness, the prediction model demonstrated good performance.ConclusionThe findings underscore that the prevalence of ametropic amblyopia in pediatric CEL patients who underwent lens surgery exhibited a marked decline over time. The prediction model established with preoperative BCVA and cardiac phenotype can provide accurate and individualized predictions of postoperative amblyopia, and it has the potential to assist ophthalmologists in rapidly identifying high-risk patients.

Patterns of intrinsic capacity trajectory and onset of activities of daily living disability among community-dwelling older adults.

Global population ageing has brought about new challenges for elderly care. Exploring intrinsic capacity (IC) over time, which is designed as a composite measure of an individual's physical and mental capabilities, is essential for promoting healthy ageing and preventing dependency, such as that emerging from disability in activities of daily living (ADL). We aimed to identify and examine the differences between classes of IC trajectory and onset of ADL disability. We conducted an observational study using data from three waves (2011-15) of the China Health and Retirement Longitudinal Study, comprising 2609 participants with 6034 observations. IC was measured by five domains, including locomotion, cognition, psychological, sensory capacities, and vitality. We used joint latent class modelling to identify distinct classes with similar patterns of IC trajectory and onset of ADL disability, as well as to explore the variation in IC trajectory and predict five-year risks of ADL disability considering the heterogeneity in the elderly population. The average baseline IC score was 7.15 (range: 0-15). We observed that IC scores slowly decreased with age, with 17.25% of participants developing ADL disability. We identified three classes of IC, which could be described as moderate health (class 1: n = 1634, 62.63%), at-risk (class 2: n = 716, 27.44%; had the highest risk of ADL disability), and optimal health (class 3: n = 259, 9.93%; had the lowest baseline risk of ADL disability). The probability of being in the moderate health class was decreased the most by emotional problems (odds ratio (OR) = 0.219; P < 0.001). Having a self-rated poor standard of living substantially reduced the chances of moderate (OR = 0.308; P = 0.001) and optimal health (OR = 0.110; P < 0.001). Observing IC trajectories and the onset of ADL disability can stratify the elderly into heterogeneous groups, as well as provide data for implementing person-centred care plans to reverse the trend and delay the adverse outcomes in clinical practice.

Development of a stereo-EEG based seizure matching system for clinical decision making in epilepsy surgery.

Objective.The proportion of patients becoming seizure-free after epilepsy surgery has stagnated. Large multi-center stereo-electroencephalography (SEEG) datasets can allow comparing new patients to past similar cases and making clinical decisions with the knowledge of how cases were treated in the past. However, the complexity of these evaluations makes the manual search for similar patients impractical. We aim to develop an automated system that electrographically and anatomically matches seizures to those in a database. Additionally, since features that define seizure similarity are unknown, we evaluate the agreement and features among experts in classifying similarity.Approach.We utilized 320 SEEG seizures from 95 consecutive patients who underwent epilepsy surgery. Eight international experts evaluated seizure-pair similarity using a four-level similarity score. As our primary outcome, we developed and validated an automated seizure matching system by employing patient data marked by independent experts. Secondary outcomes included the inter-rater agreement (IRA) and features for classifying seizure similarity.Main results.The seizure matching system achieved a median area-under-the-curve of 0.76 (interquartile range, 0.1), indicating its feasibility. Six distinct seizure similarity features were identified and proved effective: onset region, onset pattern, propagation region, duration, extent of spread, and propagation speed. Among these features, the onset region showed the strongest correlation with expert scores (Spearman's rho = 0.75,p< 0.001). Additionally, the moderate IRA confirmed the practicality of our approach with an agreement of 73.9% (7%), and Gwet's kappa of 0.45 (0.16). Further, the interoperability of the system was validated on seizures from five centers.Significance.We demonstrated the feasibility and validity of a SEEG seizure matching system across patients, effectively mirroring the expertise of epileptologists. This novel system can identify patients with seizures similar to that of a patient being evaluated, thus optimizing the treatment plan by considering the results of treating similar patients in the past, potentially improving surgery outcome.

Sleep patterns in adolescents and associations with substance use

ObjectivesGood sleep during adolescence is crucial for maintaining physical and psychological health; however, sleep disturbance during this period may contribute to health risks, such as substance use. This study aimed to identify the latent sleep patterns across male and female adolescents, and their association with drug use. MethodA cross-sectional study was conducted involving 1391 high school students (aged 15-17; 56.4% female). Participants completed the brief Pittsburgh Sleep Quality Index alongside other sleep measures, and the Timeline Follow-Back and Drug Use History Questionnaire to measure substance use. A multiple-group latent class analysis was used to identify sleep patterns across sexes, and pairwise Logistic Regression models to compare their association with substance use. ResultsFour sleep patterns were identified with varying degrees of sleep difficulties: "Good Sleep" (43.3%), "Night Awakenings" (31.8%), "Poor Efficiency and Sleep Onset" (9.4%), and "Poor Sleep" (15.5%). Female adolescents were more likely to belong to Poor Sleep and Poor Efficiency and Sleep Onset patterns, and male adolescents to Good Sleep. Likewise, binge drinking and using alcohol for a longer period were associated with experiencing Poor Efficiency and Sleep Onset (OR=1.03 and 2.3, respectively); smoking tobacco within the past month was linked to Night Awakenings (OR=2.2); and using cannabis or illegal drugs to the Poor Sleep pattern (OR=2.4 and 2.6, respectively). ConclusionsVaried sleep difficulties exist among adolescents that significantly correlate with different aspects of drug use. Targeted interventions that address both sleep and drug prevention are recommended.

Patterns of ictal surface EEG in occipital seizures: A simultaneous scalp and intracerebral recording study

ObjectiveTo describe the ictal scalp EEG patterns of occipital seizures (OS) and their spatiotemporal correlations with intracerebral occipital ictal discharges derived from simultaneous SEEG-EEG recordings. MethodsPatients with SEEG confirmed OS (14 OS from 8 patients) were selected from an epilepsy surgery center and were monitored 3–10 days using simultaneous scalp EEG and SEEG recordings. ResultsOn scalp EEG, the most common onset patterns were background activity suppression (28.6 %) and high amplitude slow wave corresponding to intracerebral DC-shift (28.6 %) and occurred with a median delay of 0 s after intra-cerebral onset. The initial discharge involved occipital electrodes in only 50 % of the seizures (7/14) with additional basal temporal (8/14) or parietal electrodes (5/14). The onset was ipsilateral to the intra-cerebral onset zone in 71.4 % of seizures and bilateral in the remaining (28.6 %). The most common propagation pattern was either unilateral (50 %) or bilateral (50 %) and a rhythmic slow activity (66.7 %). Different OS subtypes display distinct scalp EEG patterns. ConclusionScalp EEG accurately determines intra-cerebral seizure onset time in OS and has good lateralizing value. However, initial scalp modification does not always involves occipital electrodes and the second modification is well lateralizing in only 50 % of seizures. SignificanceThis study describes will help clinicians to better identify OS during video EEG and better plan intra-cerebral explorations for epilepsy surgery.

Seasonality in mood disorders: Probing association of accelerometer-derived physical activity with daylength and solar insolation

Mood disorders are the leading cause of disability worldwide. Up to 30 percent of individuals with major depressive disorder (MDD) and bipolar disorder (BD) display a seasonal pattern of onset, a phenomenon now recognized in the official diagnostic manuals (DSM-5 and ICD-11). Very little is known about the influence of day length (photoperiod) and sunlight intensity (solar insolation) on seasonal patterns in MDD and BD. Here we report a quantitative approach to examine the relationship between sunlight measures and objectively measured motor activity patterns to understand environmental factors driving seasonality in MDD and BD. Our generalized linear model (GLM) assessment of the Depresjon dataset, which includes short-term (up to two weeks) motor activity recordings of 23 unipolar and bipolar depressed patients and 32 healthy controls recruited to the study at the University of Bergen Norway (60.4° N latitude, 5.3° E longitude), revealed significant association of accelerometer-derived daytime physical activity with participant’s depressed state (p&lt;0.001), photoperiod (p&lt;0.001), and solar insolation (p&lt;0.001). Our study presents a generalizable strategy to decipher the complex interplay between sunlight, physical activity, and depressed state using open-source digital tools. The ability to identify mood disturbances, particularly in seasonally susceptible individuals, using passive digital biomarker data offers great promise in informing next-generation predictive, personalized diagnostics in mental health.

The development of depression and social anxiety symptoms in adolescents and the negative impact of the COVID-19 pandemic and desire for peer contact.

Adolescence is a dynamic developmental phase in which contact with peers is crucial for socio-emotional development and wellbeing. Depression and social anxiety show patterns of high onset during this period, and more for girls than boys. Here we examine this development among Dutch adolescents, as well as how desire for more peer contact as a result of social distancing measures during the COVID-19 pandemic contributed to this increase. We used a longitudinal three-wave design to examine 406 typically developing Dutch adolescents across two consecutive cohorts; Cohort 1: 2016-2019 (N = 138, 53.6% girls, age at T0 M = 13.00, SD = 0.42), Cohort 2: 2017-2020 (N = 268, 63.1% girls, age at T0 M = 13.05, SD = 0.39), final wave during spring 2020 during the first COVID-19 lockdown. Self-report questionnaires were used to measure depression and social anxiety symptoms, desire for change in the amount of peer contact during lockdowns, and emotion regulation. Parallel process dual latent growth models and autoregressive cross-lagged models were used to test the hypotheses. Results showed that symptoms of both depression and social anxiety increase during adolescence. Gender analysis reveal a higher initial level and increase in depression symptoms for girls, while levels for boys decreased. Adolescents exposed to the pandemic showed a steeper increase in depression but not in social anxiety. Desire for more peer contact was related to an increase in depression and social anxiety, though only in girls. No evidence was found for moderation of emotion regulation skills concerning COVID evoked emotions on the association between desire for peer contact and anxiety and depression symptom development. Symptoms of social anxiety increased during adolescence in boys and girls. Symptoms of depression increased for girls, but decreased for boys. The increase in depression was greater in a cohort who experienced the COVID-19 pandemic. For girls, a desire for more peer contact was associated with an increase of depression and social anxiety symptoms in times of social restrictions.

Examining the onset and cessation patterns of active smoking among college students: an interpretative analysis

Smoking is a prevalent global issue, with a significant risk factor for various non-communicable diseases necessitating prolonged, costly, and potentially devastating medical treatments. In addition, infectious diseases such as tuberculosis, COVID-19, and pneumonia in toddlers are often associated with active and passive smoking habits. The correlation is evident across diverse demographics, encompassing individuals of varying ages, professions, and genders. Therefore, this research aimed to explore and describe behavior of active smokers among campus members at various universities, focusing on the initiation, cessation, and influencing factors associated with smoking.A qualitative research design was used with a hermeneutic phenomenological approach, where information was provided by five active smoker informants.These individuals started smoking as teenagers, and the fluctuating patterns were influenced by health concerns or a perceived lack of significance attributed to smoking. However, the periods of abstinence were only temporary due to the pervasive influence of social and environmental factors. The initiation of smoking commonly started from the influence of close acquaintances, such as family members. Meanwhile, the process of quitting encountered numerous obstacles, primarily from potent social factors outweighing personal intentions.The implementation of smoking cessation strategies posed challenges due to the profound impacts of addiction, requiring unwavering determination, comprehensive plans, and diligent efforts.

Analysis of Atypical Antipsychotics-Induced Adverse Events Related to Diabetes Mellitus in Patients With Dementia Using the Japanese Adverse Drug Event Report Database.

Patients with dementia are prescribed low-dose atypical antipsychotics (AAPs) to treat psycho-behavioral symptoms. Although AAPs are known to cause diabetes mellitus-related adverse events (DMAEs), information regarding AAPs-induced DMAEs experienced by patients with dementia is lacking. To use the Japan Adverse Drug Event Report (JADER) database to assess the onset tendencies and patterns of DMAEs attributable to AAPs prescribed to patients with dementia. We performed an analysis using dementia cases from the JADER database that were registered from April 2004 to December 2022. Data in the JADER database are completely anonymized; thus, we did not require institutional review board approval for using the JADER database in our study. The reporting odds ratio and proportional reporting ratio (PRR) were used to assess the onset tendencies of DMAEs with AAPs. In addition, Weibull shape parameters were used to assess the patterns of DMAEs that occur with the use of AAPs. We identified AAPs associated with DMAEs. In particular, low doses of quetiapine showed the potential to induce DMAEs. An analysis of the onset of DMAEs showed the early failure patterns for AAPs (median onset = 38 days). The AAPs may cause DMAEs in patients with dementia. Low doses of quetiapine may induce DMAEs. Health care workers should focus on the development of DMAEs during the early administration period of AAPs. These results may assist with the safe management of patients with dementia who use AAPs.

Floral ontogeny reveals potential synapomorphies for Senegalia sect. Monacanthea p.p. (Leguminosae).

Senegalia was recently described as non-monophyletic; however, its sections exhibit robust monophyletic support, suggesting a potential reclassification into separate genera-Senegalia sect. Monocanthea p.p. is the largest section. It contains 164 species of pantropical distribution and includes all of the current 99 neotropical species of Senegalia; however, no morphological characteristics are available to differentiate this section. To characterize this section, we examined floral developmental traits in four species of Senegalia sect. Monocanthea p.p. These traits were previously considered as potentially distinguishing features within Acacia s.l. and include the onset patterns of the androecium, the timing of calyx union, the origin of the staminal disc, and the presence of stomata on the petals. Furthermore, we analyzed previously unexplored traits, such as corolla union types, inflorescence development, and micromorphological features related to the indumentum, as well as the presence and location of stomata. The characteristics proposed as potential synapomorphies of the group include the postgenital fusion of the corolla and the presence of a staminal disc formed at the base of the filaments. The other analyzed floral characteristics were not informative for the characterization of the group. Future studies of floral ontogeny will help to establish more precise patterns, mainly whether corolla union and staminal tube formation occur similarly in African and Asian sections of Senegalia.

Seizure onset and offset pattern determine the entrainment of the cortex and substantia nigra in the nonhuman primate model of focal temporal lobe seizures.

Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy. A major focus of human and animal studies on TLE network has been the limbic circuit. However, there is also evidence suggesting an active role of the basal ganglia in the propagation and control of temporal lobe seizures. Here, we characterize the involvement of the substantia nigra (SN) and somatosensory cortex (SI) during temporal lobe (TL) seizures induced by penicillin injection in the hippocampus (HPC) of two nonhuman primates. The seizure onset and offset patterns were manually classified and spectral power and coherence were calculated. We then compared the 3-second segments recorded in pre-ictal, onset, offset and post-ictal periods based on the seizure onset and offset patterns. Our results demonstrated an involvement of the SN and SI dependent on the seizure onset and offset pattern. We found that low amplitude fast activity (LAF) and high amplitude slow activity (HAS) onset patterns were associated with an increase in activity of the SN while the change in activity was limited to LAF seizures in the SI. However, the increase in HPC/SN coherence was specific to the farther-spreading LAF onset pattern. As for the role of the SN in seizure cessation, we observed that the coherence between the HPC/SN was reduced during burst suppression (BS) compared to other termination phases. Additionally, we found that this coherence returned to normal levels after the seizure ended, with no significant difference in post-ictal periods among the three types of seizure offsets. This study constitutes the first demonstration of TL seizures entraining the SN in the primate brain. Moreover, these findings provide evidence that this entrainment is dependent on the onset and offset pattern and support the hypothesis that the SN might play a role in the maintenance and termination of some specific temporal lobe seizure.

Web-based survey on injuries among ultimate frisbee athletes in Japanese college sports: sex differences in injury location and onset

BackgroundUltimate Frisbee (Ultimate) has gained significant popularity. However, a comprehensive understanding of injury characteristics, including sex differences in injury location and onset, remains unclear. This study aimed to investigate the injury profile of male and female athletes using data from the Japanese University Athletic Association survey.MethodsData were collected through a web-based survey conducted between June and October 2022, focusing on injuries sustained within the past year. Athletes provided detailed information, including injury location, severity, and onset pattern. This study utilized data collected through the UNIVAS survey, offering insights into the injury landscape among female Ultimate athletes. The study examined factors influencing lower limb injuries, including training days and the nature of contact during play.ResultsA total of 116 athletes participated in the survey with 57 (49.1%) reporting injuries, of which 42 injuries involved the lower limbs. Lower-extremity injuries exhibited a higher likelihood of occurrence in female compared to male athletes (p = 0.05, φ = 0.18). Athletes with lower limb injuries demonstrated significantly more training days (p = 0.01, Cohen’s d = 0.76). Non-contact injuries were more prevalent than contact injuries (p < 0.01, φ = 0.53), with non-contact injuries often causing prolonged interruptions in competition.ConclusionsFemale Ultimate athletes experienced a high frequency of severe lower extremity injuries, particularly those stemming from non-contact incidents. More training days were an independent factor associated with these outcomes.

The Clinical Course of the Late Toxicity of Definitive Radiotherapy in Cervical Cancer.

Background and Objectives: This study aimed to investigate the clinical course and characteristics of late toxicity over time following the completion of definitive radiotherapy (RT) in patients with cervical cancer. Materials and Methods: We retrospectively reviewed the medical records of 60 patients with cervical cancer who underwent pelvic external beam radiotherapy followed by intracavitary brachytherapy. Late toxicity was assessed for the lower gastrointestinal (GI) tract and bladder organ at 6, 12, 24, 36, and >36 months post-RT. We examined the onset and prevalence of late toxicity at each time point. Clinical remission and interventions for managing late toxicity were also investigated. Results: The peak onset of lower GI toxicity occurred 12 months after RT completion, with a median symptom duration of 9.9 months (range, 0.1-26.3 months), and exhibited its highest prevalence rate of 15.5% at 24 months post-RT. Most GI toxicities developed and resolved within three years post-RT, with a prevalence rate of 8.1% at three years, followed by a decreasing trend. Bladder toxicity first peaked at 24 months post-RT and continued to occur beyond 36 months, showing the re-increasing pattern in the prevalence rate after 36 months (23.5%). In terms of clinical remission, 66.7% of lower GI toxicities (12 of 18 patients) and 60% of bladder toxicities (9 of 15 patients) achieved complete remission by the last follow-up date. Conclusions: Late toxicities of the GI and bladder following definitive RT in cervical cancer are partially reversible and exhibit distinct patterns of onset and prevalence over time. A systematic follow-up strategy should be established for the early detection and timely intervention of late toxicity by understanding these clinical courses.

Investigating current clinical opinions in stereoelectroencephalography-informed epilepsy surgery.

Stereoelectroencephalography (SEEG) is increasingly utilized worldwide in epilepsy surgery planning. International guidelines for SEEG terminology and interpretation are yet to be proposed. There are worldwide differences in SEEG definitions, application of features in epilepsy surgery planning, and interpretation of surgical outcomes. This hinders the clinical interpretation of SEEG findings and collaborative research. We aimed to assess the global perspectives on SEEG terminology, differences in the application of presurgical features, and variability in the interpretation of surgery outcome scores, and analyze how clinical expert demographics influenced these opinions. We assessed the practices and opinions of epileptologists with specialized training in SEEG using a survey. Data were qualitatively analyzed, and subgroups were examined based on geographical regions and years of experience. Primary outcomes included opinions on SEEG terminology, features used for epilepsy surgery, and interpretation of outcome scores. Additionally, we conducted a multilevel regression and poststratification analysis to characterize the nonresponders. A total of 321 expert responses from 39 countries were analyzed. We observed substantial differences in terminology, practices, and use of presurgical features across geographical regions and SEEG expertise levels. The majority of experts (220, 68.5%) favored the Lüders epileptogenic zone definition. Experts were divided regarding the seizure onset zone definition, with 179 (55.8%) favoring onset alone and 135 (42.1%) supporting onset and early propagation. In terms of presurgical SEEG features, a clear preference was found for ictal features over interictal features. Seizure onset patterns were identified as the most important features by 265 experts (82.5%). We found similar trends after correcting for nonresponders using regression analysis. This study underscores the need for standardized terminology, interpretation, and outcome assessment in SEEG-informed epilepsy surgery. By highlighting the diverse perspectives and practices in SEEG, this research lays a solid foundation for developing globally accepted terminology and guidelines, advancing the field toward improved communication and standardization in epilepsy surgery.

Temporal lobe epilepsy page: Role of temporal lobe structures and subjacent pathology in the intracranial ictal onset pattern in pediatric patients with temporal lobe epilepsy: A stereo-electroencephalogram analysis

ObjectiveTo determine the intracranial ictal onset and early spread patterns in pediatric patients with Temporal lobe epilepsy and its possible association with histopathology, temporal structure involved, mesial structural pathology, and possible implication in postsurgical outcome. MethodsA descriptive, retrospective, cross-sectional study was carried out in a group of children from Children’s Wisconsin between 2016 and 2022. ResultsThis study showed a strong association between ictal onset patterns and underlying histology (p < 0.05). Low-Frequency High Amplitude periodic spikes were seen only in patients with HS (20.6 %). A strong statistically significant association was found between different ictal onset patterns and the temporal lobe structure involved in the ictal onset (p < 0.001). Seizures with ictal onset consisting of Slow Potential Shift with superimposed Low Voltage Fast Activity arise from the Inferior Temporal Lobe or Middle Temporal Gyrus in a more significant proportion of seizures than those that originated from mesial temporal structures (Difference of proportion; p < 0.05). Low Voltage Fast Activity periodic spikes as an ictal pattern were seen in a patient with seizures arising outside the mesial temporal structure. The most frequent early spread pattern observed was Low Voltage Fast Activity (89.4 %); this pattern did not depend on the type of mesial structure pathology. Ictal onset patterns were associated with postsurgical outcomes (p < 0.001). The ictal onset pattern depends on the histopathology in the ictal onset zone and the temporal lobe structure involved in the ictal onset (p = 0.001). ConclusionsIntracranial ictal onset patterns in TEMPORAL LOBE EPILEPSY depend on underlying histology and the temporal lobe structure involved in its onset.

A susceptibility gene signature for ERBB2-driven mammary tumour development and metastasis in collaborative cross mice

Deeper insights into ERBB2-driven cancers are essential to develop new treatment approaches for ERBB2+ breast cancers (BCs). We employed the Collaborative Cross (CC) mouse model to unearth genetic factors underpinning Erbb2-driven mammary tumour development and metastasis. 732 F1 hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains were monitored for mammary tumour phenotypes. GWAS pinpointed SNPs that influence various tumour phenotypes. Multivariate analyses and models were used to construct the polygenic score and to develop a mouse tumour susceptibility gene signature (mTSGS), where the corresponding human ortholog was identified and designated as hTSGS. The importance and clinical value of hTSGS in human BC was evaluated using public datasets, encompassing TCGA, METABRIC, GSE96058, and I-SPY2 cohorts. The predictive power of mTSGS for response to chemotherapy was validated invivo using genetically diverse MMTV-Erbb2 mice. Distinct variances in tumour onset, multiplicity, and metastatic patterns were observed in F1-hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains. Besides lung metastasis, liver and kidney metastases emerged in specific CC strains. GWAS identified specific SNPs significantly associated with tumour onset, multiplicity, lung metastasis, and liver metastasis. Multivariate analyses flagged SNPs in 20 genes (Stx6, Ramp1, Traf3ip1, Nckap5, Pfkfb2, Trmt1l, Rprd1b, Rer1, Sepsecs, Rhobtb1, Tsen15, Abcc3, Arid5b, Tnr, Dock2, Tti1, Fam81a, Oxr1, Plxna2, and Tbc1d31) independently tied to various tumour characteristics, designated as a mTSGS. hTSGS scores (hTSGSS) based on their transcriptional level showed prognostic values, superseding clinical factors and PAM50 subtype across multiple human BC cohorts, and predicted pathological complete response independent of and superior to MammaPrint score in I-SPY2 study. The power of mTSGS score for predicting chemotherapy response was further validated in an invivo mouse MMTV-Erbb2 model, showing that, like findings in human patients, mouse tumours with low mTSGS scores were most likely to respond to treatment. Our investigation has unveiled many new genes predisposing individuals to ERBB2-driven cancer. Translational findings indicate that hTSGS holds promise as a biomarker for refining treatment strategies for patients with BC. The U.S. Department of Defense (DoD) Breast Cancer Research Program (BCRP) (BC190820), United States; MCIN/AEI/10.13039/501100011039 (PID2020-118527RB-I00, PDC2021-121735-I00), the "European Union Next Generation EU/PRTR," the Regional Government of Castile and León (CSI144P20), European Union.

The impact of residential environment on stroke onset and its spatial heterogeneity: A multiscale exploration in Shanghai

BackgroundStroke is a worldwide concern due to its high disability and mortality rates, especially in many countries entering ageing societies. This study aims to understand the spatial heterogeneity of stroke onset and residential environment influence scopes from multiscale. MethodsThe 2013 to 2022 spatiotemporal distribution pattern of stroke onset was obtained via out-patient data from a hospital in Shanghai. Then nine residential environmental factors were selected to estimate the association of stroke onset by multiscale geographically weighted regression (MGWR), in three scenarios. ResultsAccessibility to pubs/bars (PUB) and building density (BD) were the top two residential environmental factors both for the entire sample and by gender. Stress-related environmental factors have a greater impact on the onset of stroke in men but are limited in scope. The population of elderly people have relevance to environmental variables heterogeneity. The indicators relating to unhealthy food and alcohol suggest that habit-inducing environmental factors have a limited impact on stroke onset, but rather that pre-existing habits play a greater role. ConclusionsMGWR analyses individual components across multiple bandwidths, revealing geographical disparities in the impact of elements that would otherwise be undetected on a global scale. Environmental factors have a limited impact on the onset of stroke. When society is faced with both heavy ageing and fiscal constraints, some of the blue-green space budgets can be scaled back to invest in more secure facilities.

Streamflow drought onset and severity explained by non‐linear responses between climate‐catchment and land surface processes

AbstractKnowledge of drought onset and its relationship with drought severity (deficit volume) is crucial for providing timely information for reservoir operations, irrigation scheduling, devising cropping choices and patterns and managing surface and groundwater water resources. An analysis of the relationship between drought onset timing and deficit volume can help in drought hazard assessments and associated risks. Despite its importance, little attention has been paid to understand the drought onset timing and its potential linkage with deficit volume for effective drought monitoring and its impact assessment. Further, only a few studies have explored the role of environmental controls, encompassing the interaction between climate, catchment and land‐surface processes in influencing streamflow droughts and associated characteristics such as onset time and severity. This study leverages quality‐controlled streamflow observations from 1965 to 2018 to unveil regional patterns of streamflow drought onset, at‐site trends in deficit volume and detect non‐linear relationships between onset timing and deficit volume across 82 rain‐fed catchments in peninsular India (8°–24° N, 72°–87° E). We show that around 12% of catchments show an earlier onset of streamflow droughts in conjunction with a decreasing trend in deficit volume. Further, approximately one‐third of the catchments show a significant non‐linear dependency between drought deficit volume and onset time. Among catchment controls, such as soil and topographic properties, we found soil organic carbon stock and stock as dominant drivers controlling the streamflow drought onset time. Likewise, sand content and vertical distance to channel network control the streamflow deficit volume. Finally, the linkages between inferred dominant low‐flow generation mechanisms and the specific combinations of environmental controls are synthesized in a conceptual diagram that might assist in developing appropriate models for low‐flow simulations and predictions, especially across ungauged sites. The new insights add value to understanding the chain of physical processes linking climatic and physiographic controls on streamflow droughts, which can support drought forecasting and climate impact assessment efforts.

Understanding the dynamics of mastitis in milk yield: decoding onset and recovery patterns in response to mastitis occurrence

No recent study attempted to model daily milk losses before and after mastitis onset and the moment when it begins. Thus, we aimed to describe the impact of mastitis on milk production based on mastitis level and moment of occurrence. We used data from 11 dairy farms, and the data set consisted of 885,759 daily individual milk test records from 3,508 cows in different lactations, with an average milk yield from January 2017 to December 2022. We modeled the impact of mastitis severity [i.e., 1 (mild) and 2 (severe)] based on the drop and recovery of milk yield following 3 steps. First, we removed milk recorded on the day of diagnosis of mastitis from the data set and fitted a Wood's Curve for each cow and parity. Second, we returned the mastitis data to the data set and estimated the residual milk loss due to mastitis from 15 d before to 30 d after the mastitis event. Third, we used generalized additive mixed effect models to estimate the residual milk loss, including farm as a random effect. In addition to the random effect of the farm, we also included the predicted value of mastitis, the day effect before and after mastitis incidence, and the interaction between the predicted value of mastitis and days. On average, mastitis level 2 resulted in a more severe milk yield drop in all represented stages of lactation (80, 170, and 260 d in milk), suggesting a higher loss close to the lactation peak, approximately 130 kg more than mastitis level 1. Moreover, the occurrence of mastitis case level 1 during early phase of lactation (DIM 80) can cause an average milk loss of 158 L and a ML 2, an average loss of 288 L. The estimations suggest that milk drop occurs 14 to 4 d before mastitis onset and can last until 15 to 25 d from the diagnosis, which would be the necessary time for a cow to reestablish their predicted milk yield. Therefore, our study brings new perspectives to investigate milk yield drop and recovery due to mastitis infections and how much mastitis can deplete and impair milk production.

Data-driven mathematical modeling of sleep consolidation in early childhood

Across early childhood development, sleep behavior transitions from a biphasic pattern (a daytime nap and nighttime sleep) to a monophasic pattern (only nighttime sleep). The transition to consolidated nighttime sleep, which occurs in most children between 2- and 5-years-old, is a major developmental milestone and reflects interactions between the developing homeostatic sleep drive and circadian system. Using a physiologically-based mathematical model of the sleep-wake regulatory network constrained by observational and experimental data from preschool-aged participants, we analyze how developmentally-mediated changes in the homeostatic sleep drive may contribute to the transition from napping to non-napping sleep patterns. We establish baseline behavior by identifying parameter sets that model typical 2-year-old napping behavior and 5-year-old non-napping behavior. Then we vary six model parameters associated with the dynamics of and sensitivity to the homeostatic sleep drive between the 2-year-old and 5-year-old parameter values to induce the transition from biphasic to monophasic sleep. We analyze the individual contributions of these parameters to sleep patterning by independently varying their age-dependent developmental trajectories. Parameters vary according to distinct evolution curves and produce bifurcation sequences representing various ages of transition onset, transition durations, and transitional sleep patterns. Finally, we consider the ability of napping and non-napping light schedules to reinforce napping or promote a transition to consolidated sleep, respectively. These modeling results provide insight into the role of the homeostatic sleep drive in promoting interindividual variability in developmentally-mediated transitions in sleep behavior and lay foundations for the identification of light- or behavior-based interventions that promote healthy sleep consolidation in early childhood.