Miracle-dz/UniFAR-FTUs huggingface dataset:
Establishment of the MGH Postpartum Psychosis Project: MGHP3

Objective Postpartum psychosis (PP) is a severe psychiatric disorder, with incomplete consensus on definition and diagnostic criteria. The Massachusetts General Hospital Postpartum Psychosis Project (MGHP3) was established to better ascertain the phenomenology of PP in a large cohort of diverse women spanning a wide geographical range (primarily in the US), including time of onset, symptom patterns, and associated comorbidities, psychiatric diagnoses pre- and post- the episode of PP, and also to identify genomic and clinical predictors of PP. This report describes the methods of MGHP3 and provides a status update. Method Data are collected from women who experienced PP within 6 months of childbirth and who provided this information within ten years of the study interview. Subject data are gathered during a one-time structured clinical interview conducted by phone, which includes administration of the Mini International Neuropsychiatric Interview for Psychotic Disorders Studies (Version 7.0.2), the MGHP3© Questionnaire, and other information including lifetime mental health history and use of psychiatric medications both prior to the episode of PP and during the subsequent time period prior to study interview. Subjects also provide a saliva sample to be processed for genomic analyses; a neuroimaging assessment is also conducted for a subset of participants. Results As of July 1, 2022, 311 subjects from 44 states and 7 countries were enrolled in MGHP3. Recruitment sources include social media, online advertisements, physician referral, community outreach, and partnership with PP advocacy groups. Conclusions The rigorous phenotyping, genetic sampling, and neuroimaging studies in this sample of women with histories of PP will contribute to better understanding of this serious illness. Findings from MGHP3 can catalyze ongoing discussions in the field regarding proper nosologic classification of PP as well as relevant treatment implications.
Clinical and imagenologic significance of the neutrophil-to-lymphocyte ratio in neuromyelitis optica spectrum disorder: A systematic review with meta-analysis

Background Recently, the neutrophil-lymphocyte ratio (NLR) has become a biomarker for assessing inflammatory stress and prognosis in different diseases. Objective We aimed to conduct a systematic review and meta-analysis to summarize the current evidence on the capacity of the NLR to serve as a biomarker in neuromyelitis optica spectrum disorder (NMOSD). Methods Through a comprehensive systematic search up to December 2021 and using the search terms "neutrophil-to-lymphocyte ratio" and "neuromyelitis optica spectrum disorder" we selected studies evaluating NLR values in NMOSD patients. A meta-analysis was planned, and a narrative synthesis was performed when this was not possible. Subgroup and sensitivity analyses were planned. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to assess certainty of the evidence. Results Six studies were included (1036 patients). A significant increase in the NLR was observed between NMOSD patients and healthy controls with high heterogeneity (MD: 1.04; 95% CI: 0.76; 1.32; I2 = 59%). Regarding NMOSD prognosis, relapse (OR: 1.33 –OR: 2.14) was evaluated as being related to NLR with low certainty. An association with Expanded Disability Status Scale (EDSS) score ≥4 (OR: 1.23 –OR: 1.43) was reported with moderate certainty. An association with the occurrence of lesions on MRI was reported with an OR of 1.52. Conclusion We found the NLR to be useful as a biomarker of NMOSD as it was significantly increased in the patient group compared to the healthy control group with high certainty. Additionally, the NLR was applicable as an indicator of poor prognosis with low to moderate certainty.
Diagnostic Value of the Air-Bone Threshold Gap in Stapes Fixation

Introduction: The Carhart notch is a well-known sign of stapes fixation. However, previous studies have reported that the Carhart notch is not specific to stapes fixation and is also present in other middle ear diseases. Therefore, this study investigated the diagnostic value of threshold gap between air conduction and bone conduction (ABG) for stapes fixation, instead of the bone conduction dip representing the Carhart notch. Methods: A total of 199 ears that underwent exploratory tympanotomy were enrolled in this retrospective study. They were categorized into three groups according to surgical findings: stapes fixation (SF), other ossicle fixation (OF), and chain disconnection (CD). Preoperative pure-tone audiograms and impedance audiograms were compared between the groups. Results: The incidence of the Carhart notch did not differ between the groups. The ABG at 2,000 Hz showed a good diagnostic performance for distinguishing between the SF and CD groups (area under the curve, AUC = 0.816, p < 0.001), but poor performance for distinguishing between the SF and OF groups (AUC = 0.662, p = 0.003). Bone conduction at 2,000 Hz showed a moderate performance for distinguishing between the SF and CD groups (AUC = 0.707, p < 0.001) and did not show statistically significant results for distinguishing between the SF and OF groups (AUC = 0.594, p = 0.080). The tympanic membrane compliance was significantly higher in the CD group than in the SF group (p = 0.001). Conclusions: The Carhart notch was not a specific finding of SF. The sensitivity and specificity of ABG ≤15 dB at 2,000 Hz for distinguishing between SF and CD were 60.4% and 89.2%, respectively. To prepare for surgical interventions in patients with conductive hearing loss but a normal tympanic membrane, clinicians should comprehensively consider these results.
Lectures on Algebraic Cycles

Preface to the second edition Introduction 1. 0-cycles on surfaces Lecture 1. Appendix. On an argument of Mumford in the theory of algebraic cycles 2. Curves on threefolds and intermediate Jacobians 3. Curves on threefolds and intermediate Jacobians - the relative case 4. K-theoretic and cohomological methods 5. Torsion in the Chow group 6. Complements on H2(K2) 7. Diophantine questions 8. Relative cycles and zeta functions 9. Relative cycles and zeta functions (continued) References Index.
Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial

Background Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. Methods In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500). Results Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. Conclusion Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.
Nonlinear oscillations, noise and chaos in neural delayed feedback

Bifurcations and complex oscillations in the human pupil light reflex (PLR) are studied. Autonomous pupil area oscillations are produced by substituting electronically controllable nonlinear feedback for the normal negative feedback of this reflex. A physiologically sound theoretical framework in which to study pupillary oscillations is developed. The model, framed as a delay-differential equation (DDE), agrees quantitatively with the simpler periodic behaviors and qualitatively with the complex behaviors. Much of the aperiodicity in the data can be ascribed to noise and transients rather than to chaos. The critical behavior of the PLR at oscillation onset is different with piecewise constant rather than smooth negative feedback. In the former, relative fluctuations in period are larger than those in amplitude, and vice versa in the latter. Properties of the time solutions and densities of a stochastic DDE are used to explain this experimental result. The Hopf bifurcation in this system is postponed by both additive and multiplicative colored noise. Theoretical insight into the behavior of stationary densities of DDE's and the origin of the postponement is given, and implications for analyzing bifurcations in neural delayed feedback systems are discussed.
Levels of interleukin 1-beta and soluble urokinase plasminogen activation factor in peri-implant sulcular fluid of cement- and screw-retained dental implants.

OBJECTIVE The present study compares interleukin 1-beta (IL-1β) and soluble urokinase plasminogen activation factor receptor (suPAR) levels in periimplant sulcular fluid (PISF) of patients with cement-retained (CR) and screw-retained (SR) implants. METHOD AND MATERIALS Patients with CR and SR implants were encompassed. Demographic data was collected and implant-related characteristics (geometry, insertion torque, loading and retention protocol, jaw location, duration in function and depth of insertion) were retrieved from records. Modified plaque index (mPI), crestal bone loss (CBL) probing depth (PD) and modified bleeding index (mBI) were measured. suPAR and IL-1β levels were assessed in PISF. Statistical comparisons were done and correlation between clinicoradiographic parameters and PISF IL-1β and suPAR were assessed. P<0.05 were judged statistically significant. RESULTS Clinical and radiographic parameters showed no difference among SR and CR implants. There was no difference PISF volume among patients with CR (0.22±0.004 μl) and screw-retained (0.19±0.005 μl) implants. Levels of IL-1β and suPAR in patients with CR and SR implants were 50.08±0.6 ng/ml and 44.6±0.08 ng/ml, and 0.28±0.05 ng/ml and 0.22±0.006 ng/ml, respectively. CONCLUSION Implants with CR or SR restorations are comparable to one another in terms of clinico-radiographic status and demonstrate IL-1β and suPAR levels within the normal range in the PISF provided oral hygiene is stringently maintained.
1.3-/spl mu/m InGaAsP-InP n-type modulation-doped strained multiquantum-well lasers

The use of n-type modulation doping to reduce the threshold current, the carrier lifetime, and the internal loss in 1.3-/spl mu/m InGaAsP-InP strained multiquantum-well (MQW) lasers is experimentally demonstrated. The threshold current density, the carrier lifetime, and the internal loss were reduced by about 33%, 36%, and 28%, respectively, as compared with an undoped MQW laser. Moreover, the turn-on delay time in the n-type modulation-doped MQW lasers with a low-leakage buried heterostructure was reduced by about 35%. These results confirm the suitability of this type of laser for use in the basic structure of a monolithic laser array used as a light source for high-density parallel optical interconnection.
Social determinants of health impact mortality from HCC and cholangiocarcinoma: a population-based cohort study

Background and Aims: The social determinants of health can pose barriers to accessing cancer screening and treatment and have been associated with cancer mortality. However, it is not clear whether area deprivation is independently associated with mortality in HCC and cholangiocarcinoma when controlling for individual-level social determinants of health. Approach and Results: The cohort included individuals over 18 years old diagnosed with HCC (N=3460) or cholangiocarcinoma (N=781) and reported to the Indiana State Cancer Registry from 2009 to 2017. Area disadvantage was measured using the social deprivation index (SDI). SDI was obtained by linking addresses to the American Community Survey. Individual social determinants of health included race, ethnicity, sex, marital status, and insurance type. The primary outcome was mortality while controlling for SDI and individual social determinants of health by means of Cox proportional hazard modeling. In HCC, living in a neighborhood in the fourth quartile of census-track SDI (most deprived) was associated with higher mortality (HR: 1.14, 95% CI, 1.003–1.30, p=0.04) than living in a first quartile SDI neighborhood. Being uninsured (HR: 1.64, 95% CI, 1.30–2.07, p<0.0001) and never being married (HR: 1.31, 95% CI, 1.15–1.48, p<0.0001) were also associated with mortality in HCC. In cholangiocarcinoma, SDI was not associated with mortality. Conclusions: Social deprivation was independently associated with mortality in HCC but not cholangiocarcinoma. Further research is needed to better understand how to intervene on both area and individual social determinants of health and develop interventions to address these disparities.
Assessing Disease Activity in Pediatric Crohn’s Disease Using Ultrasound: The Pediatric Crohn Disease Intestinal Ultrasound Score

Objectives: Currently, there is no consensus on how to score Crohn disease (CD) activity assessed by intestinal ultrasound (IUS) in children. This study aimed to design an easy-to-use IUS score for disease activity in pediatric CD. Methods: Children undergoing ileo-colonoscopy for CD assessment underwent IUS the day before ileo-colonoscopy, assessed with simple endoscopic score for CD (SES-CD). IUS features were compared to the SES-CD on segmental level. Multiple regression analyses, separately for terminal ileum (TI) and colon, were done to assess predictors of disease activity and to develop a model. Results: In 74 CD patients (median 15 years, 48% female), 67 TI and 364 colon segments were assessed. Based on receiver operating characteristics curves, bowel wall thickness (BWT) was categorized into low [1 point: 2–3 mm (TI) and 1.6–2 mm (colon)], medium [2 points: 3.0–3.7 mm (TI) and 2.0–2.7 mm (colon)], and high [3 points: >3.7 mm (TI) and >2.7 mm (colon)]. In TI, only BWT was retained in the model [high BWT: odds ratio (OR) 11.50, P < 0.001]. In colon, BWT (high BWT: OR 8.63, P < 0.001) and mesenteric fat (1 point: OR 3.02, P < 0.001) were independent predictors. A pediatric Crohn disease IUS score (PCD-US) cut-off of 1 resulted in a sensitivity of 82% (95% confidence interval, CI: 65%–93%) and 85% (95% CI: 80%–89%) and a cut-off of 3 in a specificity of 88% (72%–97%) and 92% (87%–96%) for TI and colon, respectively. Inter-observer agreement was moderate for TI and colon (K: 0.42, K: 0.49, respectively). Conclusions: The PCD-US score is an easy-to-use and reliable score to detect or rule out CD activity on segmental level in children. External validation is needed before applying this score in clinical practice.
Stomatal behavior moderates water cost of CO2 acquisition for 21 boreal and temperate species under experimental climate change.

The linkage of stomatal behavior with photosynthesis is critical to understanding water and carbon cycles under global change. The relationship of stomatal conductance (gs ) and CO2 assimilation (Anet ) across a range of environmental contexts, as represented in the model parameter (g1 ), has served as a proxy of the marginal water cost of carbon acquisition. We use g1 to assess species differences in stomatal behavior to a decade of open-air experimental climate change manipulations, asking whether generalizable patterns exist across species and climate contexts. Anet -gs measurements (17,727) for 21 boreal and temperate tree species under ambient and +3.3°C warming, and ambient and ~40% summer rainfall reduction, provided >2,700 estimates of g1 . Warming and/or reduced rainfall treatments both lowered g1 because those treatments resulted in lower soil moisture, and because stomatal behavior changed more in warming when soil moisture was low. Species tended to respond similarly, although in species from warmer and drier habitats g1 tended to be slightly higher and to be the least sensitive to the decrease in soil water. Overall, both warming and rainfall reduction consistently made stomatal behavior more conservative in terms of water loss per unit carbon gain across 21 species and a decade of experimental observation. This article is protected by copyright. All rights reserved.
Thermal Postbuckling Analysis of 3D Braided Composite Cylindrical Shells

Thermal postbuckling analysis is presented for 3D braided composite cylindrical shell of finite length subjected to a uniform temperature rise. Based on a micro-macro-mechanical model, a 3D braided composite may be as a cell system and the geometry of each cell is deeply dependent on its position in the cross-section of the cylindrical shell. The material properties of epoxy are expressed as a linear function of temperature. The governing equations are based on Reddy's higher order shear deformation shell theory with a von Karman-Donnell-type of kinematic nonlinearity and including thermal effects. A singular perturbation technique is employed to determine the buckling temperatures and postbuckling behaviors of 3D braided composite cylindrical shells. The numerical illustrations concern the postbuckling behavior of perfect and imperfect, braided composite cylindrical shells with different values of geometric parameter and of fiber volume fraction. The results show that the shell has lower buckling temperatures and postbuckling equilibrium paths when the temperature-dependent properties are taken into account. The results reveal that the fiber volume fraction, braiding angle and the shell geometric parameter have a significant effect on the thermal buckling and postbuckling behavior of braided composite cylindrical shells.
Estrous cycle impacts on dendritic spine plasticity in rat nucleus accumbens core and shell and caudate–putamen

An important factor that can modulate neuron properties is sex‐specific hormone fluctuations, including the human menstrual cycle and rat estrous cycle in adult females. Considering the striatal brain regions, the nucleus accumbens (NAc) core, NAc shell, and caudate–putamen (CPu), the estrous cycle has previously been shown to impact relevant behaviors and disorders, neuromodulator action, and medium spiny neuron (MSN) electrophysiology. Whether the estrous cycle impacts MSN dendritic spine attributes has not yet been examined, even though MSN spines and glutamatergic synapse properties are sensitive to exogenously applied estradiol. Thus, we hypothesized that MSN dendritic spine attributes would differ by estrous cycle phase. To test this hypothesis, brains from adult male rats and female rats in diestrus, proestrus AM, proestrus PM, and estrus were processed for Rapid Golgi–Cox staining. MSN dendritic spine density, size, and type were analyzed in the NAc core, NAc shell, and CPu. Overall spine size differed across estrous cycle phases in female NAc core and NAc shell, and spine length differed across estrous cycle phase in NAc shell and CPu. Consistent with previous work, dendritic spine density was increased in the NAc core compared to the NAc shell and CPu, independent of sex and estrous cycle. Spine attributes in all striatal regions did not differ by sex when estrous cycle was disregarded. These results indicate, for the first time, that estrous cycle phase impacts dendritic spine plasticity in striatal regions, providing a neuroanatomical avenue by which sex‐specific hormone fluctuations can impact striatal function and disorders.
Pharmacogenomics in Asians: Differences and similarities with other human populations

ABSTRACT Introduction Various pharmacogenomic (PGx) variants differ widely in different ethnicities. and clinical outcomes associated with these variants may also be substantially varied. Literature was searched in different databases, i.e. PubMed, ScienceDirect, Web of Science, and PharmGKB, from inception to 30 June 2022 for this review. Areas covered Certain PGx variants were distinctly varied in Asian populations compared to the other human populations, e.g. CYP2C19*2,*3,*17; CYP2C9*2,*3; CYP2D6*4,*5,*10,*41; UGT1A1*6,*28; HLA-B*15:02, HLA-B*15:21, HLA-B*58:01, and HLA-A*31:01. However, certain other variants do not vary greatly between Asian and other ethnicities, e.g. CYP3A5*3; ABCB1, and SLCO1B1*5. As evident in this review, the risk of major adverse cardiovascular events (MACE) was much stronger in Asian patients taking clopidogrel and who inherited the CYP2C19 loss-of-function alleles, e.g. CYP2C19*2 and*3, when compared to the western/Caucasian patients. Additionally, the risk of carbamazepine-induced severe cutaneous adverse drug reactions (SCARs) for the patients inheriting HLA-B*15:02 and HLA-B*15:21 alleles varied significantly between Asian and other ethnicities. In contrast, both Caucasian and Asian patients inheriting the SLCO1B1*5 variant possessed a similar magnitude of muscle toxicity, i.e. myopathy. Expert opinion Asian countries should take measures toward expanding PGx research, as well as initiatives for the purposes of obtaining clinical benefits from this newly evolving and economically viable treatment model.
CD70 and PD‐L1 (CD274) co‐expression predicts poor clinical outcomes in patients with pleural mesothelioma

Diffuse pleural mesothelioma (PM) is a highly aggressive tumour typically associated with short survival. Recently, the effectiveness of first‐line immune checkpoint inhibitors in patients with unresectable PM was reported. CD70–CD27 signalling plays a co‐stimulatory role in promoting T cell expansion and differentiation through the nuclear factor κB (NF‐κB) pathway. Conversely, the PD‐L1 (CD274)–PD‐1 (PDCD1) pathway is crucial for the modulation of immune responses in normal conditions. Nevertheless, pathological activation of both the CD70–CD27 and PD‐L1–PD‐1 pathways by aberrantly expressed CD70 and PD‐L1 participates in the immune evasion of tumour cells. In this study, 171 well‐characterised PMs including epithelioid (n = 144), biphasic (n = 15), and sarcomatoid (n = 12) histotypes were evaluated immunohistochemically for CD70, PD‐L1, and immune cell markers such as CD3, CD4, CD8, CD56, PD‐1, FOXP3, CD68, and CD163. Eight percent (14/171) of mesotheliomas simultaneously expressed CD70 and PD‐L1 on the tumour cell membrane. PMs co‐expressing CD70 and PD‐L1 contained significantly higher numbers of CD8+ (p = 0.0016), FOXP3+ (p = 0.00075), and CD163+ (p = 0.0011) immune cells within their microenvironments. Overall survival was significantly decreased in the cohort of patients with PM co‐expressing CD70 and PD‐L1 (p < 0.0001). In vitro experiments revealed that PD‐L1 and CD70 additively enhanced the motility and invasiveness of PM cells. In contrast, PM cell proliferation was suppressed by PD‐L1. PD‐L1 enhanced mesenchymal phenotypes such as N‐cadherin up‐regulation. Collectively, these findings suggest that CD70 and PD‐L1 both enhance the malignant phenotypes of PM and diminish anti‐tumour immune responses. Based on our observations, combination therapy targeting these signalling pathways might be useful in patients with PM.