Adaptation to photoperiod via dynamic neurotransmitter segregation.

Changes in the amount of daylight (photoperiod) alter physiology and behaviour1,2. Adaptive responses to seasonal photoperiods are vital to all organisms-dysregulation associates with disease, including affective disorders3 and metabolic syndromes4. The circadian rhythm circuitry is implicated in such responses5,6, yet little is known about the precise cellular substrates that underlie phase synchronization to photoperiod change. Here we identify a brain circuit and system of axon branch-specific and reversible neurotransmitter deployment that are critical for behavioural and sleep adaptation to photoperiod. A type of neuron called mrEn1-Pet17 in the mouse brainstem median raphe nucleus segregates serotonin from VGLUT3 (also known as SLC17A8, a proxy for glutamate) to different axonal branches that innervate specific brain regions involved in circadian rhythm and sleep-wake timing8,9. This branch-specific neurotransmitter deployment did not distinguish between daylight and dark phase; however, it reorganized with change in photoperiod. Axonal boutons, but not cell soma, changed neurochemical phenotype upon a shift away from equinox light/dark conditions, and these changes were reversed upon return to equinox conditions. When we genetically disabled Vglut3 in mrEn1-Pet1 neurons, sleep-wake periods, voluntary activity and clock gene expression did not synchronize to the new photoperiod or were delayed. Combining intersectional rabies virus tracing and projection-specific neuronal silencing, we delineated a preoptic area-to-mrEn1Pet1 connection that was responsible for decoding the photoperiodic inputs, driving the neurotransmitter reorganization and promoting behavioural synchronization. Our results reveal a brain circuit and periodic, branch-specific neurotransmitter deployment that regulates organismal adaptation to photoperiod change.

Cranial bone microarchitecture in a mouse model for syndromic craniosynostosis.

Crouzon syndrome is a congenital craniofacial disorder caused by mutations in the Fibroblast Growth Factor Receptor 2 (FGFR2). It is characterized by the premature fusion of cranial sutures, leading to a brachycephalic head shape, and midfacial hypoplasia. The aim of this study was to investigate the effect of the FGFR2 mutation on the microarchitecture of cranial bones at different stages of postnatal skull development, using the FGFR2C342Y mouse model. Apart from craniosynostosis, this model shows cranial bone abnormalities. High-resolution synchrotron microtomography images of the frontal and parietal bone were acquired for both FGFR2C342Y/+ (Crouzon, heterozygous mutant) and FGFR2+/+ (control, wild-type) mice at five ages (postnatal days 1, 3, 7, 14 and 21, n = 6 each). Morphometric measurements were determined for cortical bone porosity: osteocyte lacunae and canals. General linear model to assess the effect of age, anatomical location and genotype was carried out for each morphometric measurement. Histological analysis was performed to validate the findings. In both groups (Crouzon and wild-type), statistical difference in bone volume fraction, average canal volume, lacunar number density, lacunar volume density and canal volume density was found at most age points, with the frontal bone generally showing higher porosity and fewer lacunae. Frontal bone showed differences between the Crouzon and wild-type groups in terms of lacunar morphometry (average lacunar volume, lacunar number density and lacunar volume density) with larger, less dense lacunae around the postnatal age of P7-P14. Histological analysis of bone showed marked differences in frontal bone only. These findings provide a better understanding of the pathogenesis of Crouzon syndrome and will contribute to computational models that predict postoperative changes with the aim to improve surgical outcome.

Nonlinearity vs nonlocality with emphasis on bandwidth broadening in semiconductor-based 1d metamaterials.

The physics of nonlinear optical materials is incredibly versatile, with the design of novel materials and structures offering numerous degrees of freedom. Nevertheless, weak inherent nonlinearity of conventional optical materials continues to hinder the progress of a number of important applications. In this study, we delve into the realm of broadband enhancement of nonlinearity within one-dimensional (1d) plasmonic metamaterials, exploring its intricate connection with nonlocality. Specifically, we introduce a phenomenological framework for quantifying the effective third-order nonlinear susceptibility of 1d multiphase plasmonic nanostructures, utilizing heavily doped semiconductors, and subsequently applying this approach using realistic material parameters. Both direct and inverse problems of nonlinearity enhancement have been addressed. Our findings demonstrate a remarkable capability to significantly augment the third-order nonlinear susceptibility across a defined frequency range, while concurrently gauging the impact of nonlocality on this enhancement.

Properties of Cosmic Deuterons Measured by the Alpha Magnetic Spectrometer.

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of the deuteron (D) flux are presented. The measurements are based on 21×10^{6} D nuclei in the rigidity range from 1.9 to 21 GV collected from May 2011 to April 2021. We observe that over the entire rigidity range the D flux exhibits nearly identical time variations with the p, ^{3}He, and ^{4}He fluxes. Above 4.5 GV, the D/^{4}He flux ratio is time independent and its rigidity dependence is well described by a single power law ∝R^{Δ} with Δ_{D/^{4}He}=-0.108±0.005. This is in contrast with the ^{3}He/^{4}He flux ratio for which we find Δ_{^{3}He/^{4}He}=-0.289±0.003. Above ∼13 GV we find a nearly identical rigidity dependence of the D and p fluxes with a D/p flux ratio of 0.027±0.001. These unexpected observations indicate that cosmic deuterons have a sizable primarylike component. With a method independent of cosmic ray propagation, we obtain the primary component of the D flux equal to 9.4±0.5% of the ^{4}He flux and the secondary component of the D flux equal to 58±5% of the ^{3}He flux.

Computational Screening of a Single-Atom Catalyst Supported by Monolayer Nb2S2C for Oxygen Reduction Reaction.

The search for high-performance catalysts to improve the catalytic activity for an oxygen reduction reaction (ORR) is crucial for developing a proton exchange membrane fuel cell. Using the first-principles method, we have performed computational screening on a series of transition metal (TM) atoms embedded in monolayer Nb2S2C to enhance the ORR activity. Through the scaling relationship and volcano plot, our results reveal that the introduction of a single Ni or Rh atom through substitutional doping into monolayer Nb2S2C yields promising ORR catalysts with low overpotentials of 0.52 and 0.42 V, respectively. These doped atoms remain intact on the monolayer Nb2S2C even at elevated temperatures. Importantly, the catalytic activity of the Nb2S2C doped with a TM atom can be effectively correlated with an intrinsic descriptor, which can be computed based on the number of d orbital electrons and the electronegativity of TM and O atoms.

Radiomics nomogram: distinguishing benign and malignant pure ground-glass nodules based on dual-layer spectral detector CT.

AIM: To investigate the value of the combined model based on spectral quantitative parameters, radiomics features, imaging and clinical features to distinguish the benign and malignant pure ground-glass nodules (pGGNs). MATERIALS AND METHODS: A retrospective analysis of 113 patients with single pGGNs who underwent non-contrast enhancement examination of the chest on dual-layer spectral detector CT (SDCT) with two weeks before surgery was performed in our hospital. These patients were randomized into training and testing cohorts. Regions of interest based on the conventional 120 kVp poly energetic image of SDCT were outlined. Then the optimal features were extracted and selected to construct radiomic model. A combined model combining vacuole sign, electron density (ED) value and the rad score of radiomics model was built by logistic regression analysis. A nomogram was built in a training cohort and the performance of the models was evaluated in the training and testing cohorts by receiver operating characteristic curves, calibration curves and decision curve analysis. RESULTS: ED value [Odds Ratio (OR):1.100; 95% confidence interval (CI):1.027-1.166)] and vacuole sign (OR:3.343; 95% CI:0.881-12.680) were independent risk factors for the malignant pGGNs in the training cohort. A combined model was constructed using radiomics features, ED value and vacuole sign. And the AUC was 0.910 (95% CI, 0.825-0.997) and 0.850 (95% CI, 0.714-0.981) in the training and testing cohorts, respectively. CONCLUSION: The combined model based on SDCT has high specificity and sensitivity for distinguishing the benign and malignant pGGNs, suggesting the model can further improve diagnostic performance, and using a nomogram is helpful for individualized predictions.

Survival Analysis as a Basis for Testing Hypotheses when Using Quantitative Ordinal Scale Disease Severity Data.

Disease severity in plant pathology is often measured by the amount of a plant or plant part that exhibits disease symptoms. This is typically assessed using a numerical scale, which allows a standardized, convenient, and quick method of rating. These scales, known as quantitative ordinal scales (QOS), divide the percentage scale into a predetermined number of intervals. There are various ways to analyze these ordinal data, with traditional methods involving the use of midpoint conversion to represent the interval. However, this may not be precise enough, as it is only an estimate of the true value. In this case, the data may be considered interval-censored, meaning that we have some knowledge of the value but not an exact measurement. This type of uncertainty is known as censoring, and techniques that address censoring, such as survival analysis (SA), use all available information and account for this uncertainty. To investigate the pros and cons of using SA with QOS measurements, we conducted a simulation based on three pathosystems. The results showed that SA almost always outperformed midpoint conversion with data analyzed using a t test, particularly when data were not normally distributed. Midpoint conversion is currently a standard procedure. In certain cases, the midpoint approach required a 400% increase in sample size to achieve the same power as the SA method. However, as the mean severity increases, fewer additional samples are needed (approximately an additional 100%), regardless of the assessment method used. Based on these findings, we conclude that SA is a valuable method for enhancing the power of hypothesis testing when analyzing QOS severity data. Future research should investigate the wider use of survival analysis techniques in plant pathology and their potential applications in the discipline.

Impact of polygenic risk score for triglyceride trajectory and diabetic complications in subjects with type 2 diabetes based on large electronic medical record data from Taiwan: a case control study.

BACKGROUND: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications. METHODS: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS. RESULTS: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively). CONCLUSIONS: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.

Nightshift work and irregular menstrual cycle: 8-year follow-up cohort study.

BACKGROUND: Irregular menstruation is a major health problem among women, although its association with nightshift work remains controversial. AIMS: To study the association between nightshift work and irregular menstrual cycle among female workers and investigate any differences according to sleep quality, working hours or obesity. METHODS: This study included female workers who underwent health examinations from 2012 to 2019. Nightshift work, working hours, sleep quality and menstrual cycles were assessed using self-administered questionnaires. Irregular menstrual cycle was defined as self-reported irregular or ≥36 days. Adjusted odds ratios and 95% confidence intervals (CIs) were calculated by multivariable logistic regression; adjusted hazard ratios (95% CIs) for incident irregular menstrual cycle were calculated by Cox proportional hazard models with time-dependent analysis. RESULTS: The study participants were 87 147 in the cross-sectional study and 41 516 in the longitudinal study. After adjusting for all covariates in the cross-sectional analyses, the odds ratio for prevalent irregular menstrual cycle among female nightshift workers versus the reference was 1.26 (95% CI 1.2-1.33). In the cohort study, the adjusted hazard ratio for incident irregular menstrual cycle among nightshift workers was 1.95 (95% CI 1.61-2.35) in the period after 6 years. No significant differences were observed among subgroups stratified by sleep quality, working hours or obesity. CONCLUSIONS: Nightshift work is associated with an increased risk of both prevalent and incident irregular menstrual cycle in female workers without significant interactions by sleep quality, working hours or obesity.

[Effect of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients underwent haploidentical stem cell transplantation].

Objective: To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT). Methods: Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q1, Q3)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test. Results: After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002). Conclusion: Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.

[Early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency].

Objective: To examine the early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency. Methods: This is a retrospective cohort study. The clinical data of 124 patients with BAV insufficiency who underwent aortic valve repair from January 2017 to June 2023 in the Department of Cardiovascular Surgery at Fuwai Hospital were analyzed retrospectively. There were 117 males and 7 females with an age of (38.1±12.7) years (range: 14 to 65 years). Depending on whether the aortic sinus was replaced or not, surgical approaches were divided into valve sparing root replacement (reimplantation, remodeling, modified remodeling) and isolated aortic valve repair (annuloplasty, isolated aortic valve leaflet repair). Perioperative and follow-up data were collected. Kaplan-Meier method was used to plot the curves of survival rate, free recurrence rate of massive aortic valve insufficiency and free re-operation rate, and Log-rank test was used for comparison between groups. Results: Among the surgeries, there were 47 cases of reimplantation, 8 cases of remodeling, 8 cases of modified remodeling, 48 cases of aortic annuloplasty (external annuloplasty in 22 cases, CV-0 annuloplasty in 26 cases), and 13 cases of isolated leaflet repair. Leaflet plication was the most used leaflet repair technique, used in 103 patients. The cardiopulmonary bypass time was (133.7±56.9) minutes (range: 48 to 461 minutes), and aortic cross-clamp time was (103.8±47.8) minutes (range: 25 to 306 minutes), with no surgical mortality. All patients underwent outpatient or telephone follow-up. The cumulative follow-up time was 340.3 person-years and the mean follow-up time was (M (IQR)) 34.0 (25.5) months (range: 3 to 76 months). The 5-year survival rate was 98.4%, the 5-year freedom from significant insufficiency rate was 93.4% and the 5-year freedom from aortic valve reoperation rate was 95.6%. The subgroup analysis revealed a significantly better freedom from the significant insufficiency rate in the aortic valve annular reduction group compared to the non-reduction group (P<0.01). Conclusions: Aortic valve repair in patients with bicuspid aortic insufficiency could obtain steady early to mid-term outcomes. Aortic annuloplasty can reduce the risk of recurrent aortic valve insufficiency in patients undergoing aortic repair.

Temporal Structures in Positron Spectra and Charge-Sign Effects in Galactic Cosmic Rays.

We present the precision measurements of 11 years of daily cosmic positron fluxes in the rigidity range from 1.00 to 41.9 GV based on 3.4×10^{6} positrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The positron fluxes show distinctly different time variations from the electron fluxes at short and long timescales. A hysteresis between the electron fluxes and the positron fluxes is observed with a significance greater than 5σ at rigidities below 8.5 GV. On the contrary, the positron fluxes and the proton fluxes show similar time variation. Remarkably, we found that positron fluxes are modulated more than proton fluxes with a significance greater than 5σ for rigidities below 7 GV. These continuous daily positron fluxes, together with AMS daily electron, proton, and helium fluxes over an 11-year solar cycle, provide unique input to the understanding of both the charge-sign and mass dependencies of cosmic rays in the heliosphere.

First Measurement of the Nuclear-Recoil Ionization Yield in Silicon at 100 eV.

We measured the nuclear-recoil ionization yield in silicon with a cryogenic phonon-sensitive gram-scale detector. Neutrons from a monoenergetic beam scatter off of the silicon nuclei at angles corresponding to energy depositions from 4 keV down to 100 eV, the lowest energy probed so far. The results show no sign of an ionization production threshold above 100 eV. These results call for further investigation of the ionization yield theory and a comprehensive determination of the detector response function at energies below the keV scale.

Improved Measurement of the Evolution of the Reactor Antineutrino Flux and Spectrum at Daya Bay.

Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.

Properties of Cosmic-Ray Sulfur and Determination of the Composition of Primary Cosmic-Ray Carbon, Neon, Magnesium, and Sulfur: Ten-Year Results from the Alpha Magnetic Spectrometer.

We report the properties of primary cosmic-ray sulfur (S) in the rigidity range 2.15 GV to 3.0 TV based on 0.38×10^{6} sulfur nuclei collected by the Alpha Magnetic Spectrometer experiment (AMS). We observed that above 90 GV the rigidity dependence of the S flux is identical to the rigidity dependence of Ne-Mg-Si fluxes, which is different from the rigidity dependence of the He-C-O-Fe fluxes. We found that, similar to N, Na, and Al cosmic rays, over the entire rigidity range, the traditional primary cosmic rays S, Ne, Mg, and C all have sizeable secondary components, and the S, Ne, and Mg fluxes are well described by the weighted sum of the primary silicon flux and the secondary fluorine flux, and the C flux is well described by the weighted sum of the primary oxygen flux and the secondary boron flux. The primary and secondary contributions of the traditional primary cosmic-ray fluxes of C, Ne, Mg, and S (even Z elements) are distinctly different from the primary and secondary contributions of the N, Na, and Al (odd Z elements) fluxes. The abundance ratio at the source for S/Si is 0.167±0.006, for Ne/Si is 0.833±0.025, for Mg/Si is 0.994±0.029, and for C/O is 0.836±0.025. These values are determined independent of cosmic-ray propagation.

Temporal Structures in Electron Spectra and Charge Sign Effects in Galactic Cosmic Rays.

We present the precision measurements of 11 years of daily cosmic electron fluxes in the rigidity interval from 1.00 to 41.9 GV based on 2.0×10^{8} electrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The electron fluxes exhibit variations on multiple timescales. Recurrent electron flux variations with periods of 27 days, 13.5 days, and 9 days are observed. We find that the electron fluxes show distinctly different time variations from the proton fluxes. Remarkably, a hysteresis between the electron flux and the proton flux is observed with a significance of greater than 6σ at rigidities below 8.5 GV. Furthermore, significant structures in the electron-proton hysteresis are observed corresponding to sharp structures in both fluxes. This continuous daily electron data provide unique input to the understanding of the charge sign dependence of cosmic rays over an 11-year solar cycle.

Precision Measurement of Reactor Antineutrino Oscillation at Kilometer-Scale Baselines by Daya Bay.

We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3} eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3} eV^{2} for the inverted mass ordering.

Differentiation between normal and abnormal kidneys using 99mTc-DMSA SPECT with deep learning in paediatric patients.

AIM: To investigate the feasibility of using deep learning (DL) to differentiate normal from abnormal (or scarred) kidneys using technetium-99m dimercaptosuccinic acid (99mTc-DMSA) single-photon-emission computed tomography (SPECT) in paediatric patients. MATERIAL AND METHODS: Three hundred and one 99mTc-DMSA renal SPECT examinations were reviewed retrospectively. The 301 patients were split randomly into 261, 20, and 20 for training, validation, and testing data, respectively. The DL model was trained using three-dimensional (3D) SPECT images, two-dimensional (2D) maximum intensity projections (MIPs), and 2.5-dimensional (2.5D) MIPs (i.e., transverse, sagittal, and coronal views). Each DL model was trained to determine renal SPECT images into either normal or abnormal. Consensus reading results by two nuclear medicine physicians served as the reference standard. RESULTS: The DL model trained by 2.5D MIPs outperformed that trained by either 3D SPECT images or 2D MIPs. The accuracy, sensitivity, and specificity of the 2.5D model for the differentiation between normal and abnormal kidneys were 92.5%, 90% and 95%, respectively. CONCLUSION: The experimental results suggest that DL has the potential to differentiate normal from abnormal kidneys in children using 99mTc-DMSA SPECT imaging.

Quantitative assessment of cerebrospinal fluid flow and volume in enlargement of the subarachnoid spaces of infancy using MRI.

BACKGROUND: The etiology of enlarged subarachnoid spaces of infancy is unknown; however, there is radiologic similarity with normal pressure hydrocephalus. Adults with normal pressure hydrocephalus have been shown to have altered cerebrospinal (CSF) flow through the cerebral aqueduct. OBJECTIVE: To explore potential similarity between enlarged subarachnoid spaces of infancy and normal pressure hydrocephalus, we compared MRI-measured CSF flow through the cerebral aqueduct in infants with enlarged subarachnoid spaces of infancy to infants with normal brain MRIs. MATERIALS AND METHODS: This was an IRB approved retrospective study. Clinical brain MRI examinations including axial T2 imaging and phase contrast through the aqueduct were reviewed for infants with enlarged subarachnoid spaces of infancy and for infants with a qualitatively normal brain MRI. The brain and CSF volumes were segmented using a semi-automatic technique (Analyze 12.0) and CSF flow parameters were measured (cvi42, 5.14). All data was assessed for significant differences while controlling for age and sex using analysis of covariance (ANCOVA). RESULTS: Twenty-two patients with enlarged subarachnoid spaces (mean age 9.0 months, 19 males) and 15 patients with normal brain MRI (mean age 18.9 months, 8 females) were included. Volumes of the subarachnoid space (P < 0.001), lateral (P < 0.001), and third ventricles (P < 0.001) were significantly larger in infants with enlarged subarachnoid spaces of infancy. Aqueductal stroke volume significantly increased with age (P = 0.005), regardless of group. CONCLUSION: CSF volumes were significantly larger in infants with enlarged subarachnoid spaces of infancy versus infants with a normal MRI; however, there was no significant difference in CSF flow parameters between the two groups.

Multitrait meta-analyses identify potential candidate genes for growth-related traits in Holstein heifers.

Understanding the underlying pleiotropic relationships among growth and body size traits is important for refining breeding strategies in dairy cattle for optimal body size and growth rate. Therefore, we performed single-trait GWAS for monthly-recorded body weight (BW), hip height, body length, and chest girth from birth to 12 mo of age in Holstein animals, followed by stepwise multiple regression of independent or lowly-linked markers from GWAS loci using conditional and joint association analyses (COJO). Subsequently, we conducted a multitrait meta-analysis to detect pleiotropic markers. Based on the single-trait GWAS, we identified 170 significant SNPs, in which 59 of them remained significant after the COJO analyses. The most significant SNP, located at BTA7:3,676,741, explained 2.93% of the total phenotypic variance for BW6 (BW at 6 mo of age). We identified 17 SNPs with potential pleiotropic effects based on the multitrait meta-analyses, which resulted in 3 additional SNPs in comparison to those detected based on the single-trait GWAS. The identified quantitative trait loci regions overlap with genes known to influence human growth-related traits. According to positional and functional analyses, we proposed HMGA2, HNF4G, MED13L, BHLHE40, FRZB, DMP1, TRIB3, and GATAD2A as important candidate genes influencing the studied traits. The combination of single-trait GWAS and meta-analyses of GWAS results improved the efficiency of detecting associated SNPs, and provided new insights into the genetic mechanisms of growth and development in Holstein cattle.