Dysbiotic signatures and diagnostic potential of gut microbial markers for inflammatory bowel disease in Korean population.

Fecal samples were collected from 640 individuals in Korea, including 523 patients with IBD (223 with Crohn's disease [CD] and 300 with ulcerative colitis [UC]) and 117 healthy controls. The samples were subjected to cross-sectional gut metagenomic analysis using 16 S rRNA sequencing and bioinformatics analysis. Patients with IBD, particularly those with CD, exhibited significantly lower alpha diversities than the healthy subjects. Differential abundance analysis revealed dysbiotic signatures, characterized by an expansion of the genus Escherichia-Shigella in patients with CD. Functional annotations showed that functional pathways related to bacterial pathogenesis and production of hydrogen sulfide (H2S) were strongly upregulated in patients with CD. A dysbiosis score, calculated based on functional characteristics, highly correlated with disease severity. Markers distinguishing between healthy subjects and patients with IBD showed accurate classification based on a small number of microbial taxa, which may be used to diagnose ambiguous cases. These findings confirm the taxonomic and functional dysbiosis of the gut microbiota in patients with IBD, especially those with CD. Taxa indicative of dysbiosis may have significant implications for future clinical research on the management and diagnosis of IBD.

Retrospective quality review of Department of Transportation (DOT) commercial drivers medical examination forms.

OBJECTIVE: This study aimed to evaluate the quality of completion among both drivers and medical examiners in filling out Commercial Driver's (CD) Medical Examination Report Forms. METHODS: This was a cross-sectional retrospective study of abstracted data from the year 2019. CD Medical Examination Report Forms, collected from a single nationally-based employer and initially reviewed by corporate medical directors, were evaluated by the study team for completeness of documentation provided by both drivers and medical examiners (MEs). Relevant findings included unanswered questions, inconsistency between responses, and lack of necessary elaboration for positive responses. RESULTS: Among 1603 examinations, MEs completed the Medical Examination Report Form incompletely or incorrectly in 30% of examinations (n = 484). Drivers inconsistently filled out their health history with elaborations 38.7% of the time. Most commonly, they failed to elaborate on positive health history responses in 28.7% of examinations, but other types of errors were noted as well. CONCLUSIONS: A considerable proportion of drivers or examiners (n = 890, 55%) failed to adequately or correctly complete CD Medical Examination Report forms.

A transparent p-type semiconductor designed via a polarizability-enhanced strongly correlated insulator oxide matrix.

Electron-transporting transparent conducting oxides (TCOs) are a commercial reality, however, hole-transporting counterparts are far more challenging because of limited material design. Here, we propose a strategy for enhancing the hole conductivity without deteriorating the band gap (Eg) and workfunction (Φ) by Cu incorporation in a strongly correlated NiWO4 insulator. The optimal Cu-doped NiWO4 (Cu0.185Ni0.815WO4) exhibits a resistivity reduction of ∼109 times versus NiWO4 as well as band-like charge transport with the hole mobility approaching 7 cm2 V-1 s-1 at 200 K, a deep Φ of 5.77 eV, and Eg of 2.8 eV. Experimental and theoretical data reveal that the strength of the electron correlation in NiWO4 is unaffected by Cu incorporation, while the promoted polarizability weakens electron-phonon coupling, promoting the formation of large polarons. Quantum dot light-emitting and oxide p/n junction devices incorporating Cu0.185Ni0.815WO4 exhibit remarkable performances, demonstrating that our approach can be deployed to discover new p-type TCOs.

Linkage between Fuz and Gpr161 genes regulates sonic hedgehog signaling during mouse neural tube development.

Sonic hedgehog (Shh) signaling regulates embryonic morphogenesis utilizing the primary cilium, the cell's antenna, which acts as a signaling hub. Fuz, an effector of planar cell polarity signaling, regulates Shh signaling by facilitating cilia formation, and the G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling. The range of phenotypic malformations observed in mice bearing mutations in either of the genes encoding these proteins is similar; however, their functional relationship has not been previously explored. This study identified the genetic and biochemical linkage between Fuz and Gpr161 in mouse neural tube development. Fuz was found to be genetically epistatic to Gpr161 with respect to regulation of Shh signaling in mouse neural tube development. The Fuz protein biochemically interacts with Gpr161, and Fuz regulates Gpr161-mediated ciliary localization, a process that might utilize ß-arrestin 2. Our study characterizes a previously unappreciated Gpr161-Fuz axis that regulates Shh signaling during mouse neural tube development.

Age-related annual changes in arterial stiffness in healthy adults: Insights from a large Korean cohort study.

BACKGROUND AND AIMS: Arterial stiffness, a known cardiovascular risk factor, is associated with increasing age and arteriosclerosis. This study examines age-related annual changes in arterial stiffness in a large cohort of healthy individuals without cardiovascular disease, hypertension, or diabetes mellitus. METHODS: The study included 195,405 Korean adults aged 30-79 years who attended a health check-up between 2006 and 2019. Arterial stiffness was assessed using brachial-ankle pulse wave velocity (baPWV), and the final cohort for the baPWV annual change analysis comprised 147,313 participants. RESULTS: The study found that baPWV values increase progressively with age in both sexes, with the most notable changes occurring in the 70-79 age group. The spread in baPWV measurements, as indicated by the interquartile ranges, generally increases with age but was particularly pronounced in women in the 50s and 60s age groups, with men showing a greater spread in the 70-79 age group. The average annual change in baPWV (ΔbaPWV) values increased from 1.48 cm/s (95 % CI: 0.80-2.16) in the 30-39 age group to 23.72 cm/s (95 % CI: 16.25-31.19) in the 70-79 age group in men. Similarly, for women, the average ΔbaPWV values increased from 1.80 cm/s (95 % CI: 0.93-2.68) to 18.51 cm/s (95 % CI: 7.18-29.85) in the 30-39 and 70-79 age groups, respectively. The study observed that arterial stiffness in men consistently increases across all age groups, whereas in women, it does not significantly increase annually before age 50 but shows a steeper rise after this age. CONCLUSIONS: This study emphasizes the progressive nature of arterial stiffness with aging in a healthy population. It highlights notable differences in the rate of progression and the distribution of baPWV between men and women, with men exhibiting a greater spread in the oldest age group.

Effect of increasing supplementation of dietary glycine on growth performance, meat quality, liver characteristics, and intestinal health in broiler chickens raised under heat stress conditions.

The current study aimed to investigate the effect of increasing supplementation of dietary glycine (Gly) on growth performance, meat quality, liver characteristics, and intestinal health in broiler chickens raised under heat stress (HS) conditions. A total of one thousand six hundred 25-d-old broiler chickens were randomly allotted to 1 of 5 dietary treatments with 8 replicates. Each replicate comprised 20 male and 20 female birds. A negative control (NC) diet was prepared to meet or exceed energy and nutrient requirement estimates, whereas a positive control (PC) diet was formulated to contain increasing concentrations of AMEn by 50 kcal/kg as well as those of digestible amino acids, total Ca, and available P by 10% compared with the respective concentrations in the NC diet. Three additional diets were prepared by supplementing the NC diet with 0.4, 0.8, or 1.6% Gly. All chickens were raised under cyclic HS conditions at 29°C ± 0.89°C for 10 h/d and 23°C ± 1.45°C for the remaining time over an 18-d feeding trial. Results indicated that broiler chickens fed the NC diet had a greater (P < 0.05) FCR than those fed the PC diet under HS conditions. Increasing supplementation of up to 1.6% Gly in diets decreased (linear, P < 0.001) FCR in broiler chickens. Increasing supplementation of dietary Gly tended to increase (linear, P = 0.070) water holding capacity in the breast meat. Increasing supplementation of dietary Gly decreased (linear, P < 0.05) serum aspartate aminotransferase concentrations and tended to decrease blood heterophil:lymphocyte (linear, P = 0.083) and liver malondialdehyde concentrations (quadratic, P = 0.084). A tendency for increased villus height (linear, P = 0.086) and a significant increase in villus height:crypt depth ratio and goblet cell numbers (linear, P < 0.05) were identified following increasing Gly supplementation. In conclusion, increasing supplementation of dietary Gly improved feed efficiency, meat quality, liver health, and intestinal morphology possibly by mitigating oxidative stress and stress response in broiler chickens raised under HS conditions.

On the Frontlines: Protecting and Advancing Gender-Affirming Care in a Hostile Sociopolitical Environment.

Since 2020, there has been a significant cultural and political backlash in the USA to growing acceptance of gender diversity and gender-affirming care. Legislative attacks, particularly targeting gender-affirming care access for transgender and gender diverse youth, have occurred in a media environment rife with misinformation and disinformation. Even in states where a ban is not enacted, we have seen significant harm caused by such misinformation and disinformation, to transgender and gender diverse patients, their families, and clinicians who provide this important and much needed care, in the form of clinic closures and disruption of services. In this hostile sociopolitical environment, we present strategies for health care organizations and workers to continue to provide this lifesaving care thoughtfully, to safeguard the protections currently in place, and to continue to advocate for patients, families, and health care staff.

Pregnant women's experiences of online prenatal education in Korea during COVID-19: a phenomenological study.

PURPOSE: This study aimed to explore the significance and insights derived from the experiences of pregnant women in Korea who participated in online prenatal education during the COVID-19 pandemic. METHODS: This study employed the hermeneutic phenomenology framework developed by Colaizzi. It involved 12 pregnant women who participated in online prenatal education provided by public health centers in Chuncheon, Korea. Data collection was achieved through in-depth interviews conducted in Korea from October 2021 to April 2022. RESULTS: In total, 51 significant statements were extracted from the interview data and then categorized into 10 themes. Finally, three categories were formed by merging similar themes. The three basic categories of participants' experiences of online prenatal education were "feeling of safety and comfort in body and mind," "frustrated by a lack of interaction," and "digital education being a double-edged sword." Pregnant women expressed ambivalence regarding the benefits and drawbacks of the online educational experience. They desired more interactive and practical learning opportunities, even as they appreciated the comfort of learning remotely. CONCLUSION: This study revealed the phenomenon of online prenatal education as an advanced form of distance-based prenatal education instead of the traditional in-person classroom. To maximize the educational effectiveness of this new format, public health center policies must address the digital literacy gap and enhance accessibility by leveraging the immersive multimedia experiences that online education offers to pregnant women. We recommend that maternal healthcare providers adopt this innovative approach to prenatal education, utilizing distance education technology to improve participation and promote immersion.

Real-Time Imaging Assessment of Stress-Induced Vascular Inflammation Using Heartbeat-Synchronized Motion Compensation.

BACKGROUND: Chronic mental stress accelerates atherosclerosis through complicated neuroimmune pathways, needing for advanced imaging techniques to delineate underlying cellular mechanisms. While histopathology, ex vivo imaging, and snapshots of in vivo images offer promising evidence, they lack the ability to capture real-time visualization of blood cell dynamics within pulsatile arteries in longitudinal studies. METHODS: An electrically tunable lens was implemented in intravital optical microscopy, synchronizing the focal plane with heartbeats to follow artery movements. ApoE-/- mice underwent 2 weeks of restraint stress before baseline imaging followed by 2 weeks of stress exposure in the longitudinal imaging, while nonstressed mice remained undisturbed. The progression of vascular inflammation was assessed in the carotid arteries through intravital imaging and histological analyses. RESULTS: A 4-fold reduction of motion artifact, assessed by interframe SD, and an effective temporal resolution of 25.2 Hz were achieved in beating murine carotid arteries. Longitudinal intravital imaging showed chronic stress led to a 6.09-fold (P=0.017) increase in myeloid cell infiltration compared with nonstressed mice. After 3 weeks, we observed that chronic stress intensified vascular inflammation, increasing adhered myeloid cells by 2.45-fold (P=0.031), while no significant changes were noted in nonstressed mice. Microcirculation imaging revealed increased circulating, rolling, and adhered cells in stressed mice's venules. Histological analysis of the carotid arteries confirmed the in vivo findings that stress augmented plaque area, myeloid cell and macrophage accumulation, and necrotic core volume while reducing fibrous cap thickness indicating accelerated plaque formation. We visualized the 3-dimensional structure of the carotid artery and 4-dimensional dynamics of the venules in the cremaster muscle. CONCLUSIONS: Dynamic focusing motion compensation intravital microscopy enabled subcellular resolution in vivo imaging of blood cell dynamics in beating arteries under chronic restraint stress in real time. This novel technique emphasizes the importance of advanced in vivo imaging for understanding cardiovascular disease.

Widespread Use of Imaging-Guided PCI in Asia: Time for Extended Application.

In recent years, a wealth of clinical data has emerged regarding intravascular imaging involving either intravascular ultrasound or optical coherence tomography. This surge in data has propelled the adoption of intravascular imaging-guided percutaneous coronary intervention (PCI) in daily clinical practice. The findings of current randomized clinical trials regarding imaging guidance have lent strong support to the benefits of intravascular imaging-guided PCI. This holds especially true for the diagnosis and treatment of complex lesions, such as left main disease, diffuse long lesions, chronic total occlusion, severely calcified lesions, bifurcations, and in-stent restenosis, as well as in high-risk patients such as those with acute myocardial infarction or chronic kidney disease. During intravascular imaging-guided PCI, operators attempt to achieve stent optimization for maximized benefits of imaging guidance. This paper provides a comprehensive review on the updated clinical data of intravascular imaging-guided PCI and intravascular ultrasound/optical coherence tomography-derived stent optimization criteria.

Complex Multi-site Stereotactic Body Re-irradiation With CT-Guided Online Adaptive Radiotherapy.

Online adaptive radiotherapy optimizes a patient's treatment plan to their daily anatomy to account for inter-fraction motion. Daily target and organ-at-risk (OAR) delineation allows for optimized treatments and has been shown to have favorable outcomes in the abdominal region. Adaptive radiotherapy also has the potential to support fine control of dose in re-irradiation to OARs. Herein, we describe a complex multi-site re-irradiation case utilizing CT-guided adaptive radiotherapy. A 46-year-old man with metastatic hepatocellular carcinoma presented for re-irradiation of four metastatic lesions to the right acetabulum, T11, S2, and a gastrosplenic lymph node (gsLN). The right acetabulum, T11, and S2 lesions previously received 20 Gy in five fractions. For the current course, he was prescribed 35 Gy (T11, right acetabulum, and gsLN) and 30 Gy (S2) in five fractions. An equivalent dose in 2 Gy fractions (EQD2) was employed to assess cumulative doses for critical OARs and guide planning. The re-irradiated lesions were treated with stereotactic body radiation therapy (SBRT), and the gsLN was treated with adaptive radiotherapy. An isotoxic approach was utilized to create the scheduled and adapted plans for the gsLN. Adapted plans were created on the patient's daily anatomy as visualized on kilovoltage cone beam computed tomography and compared against the scheduled plan. Dose-volume histogram objectives were used to compare the plans, and the superior plan was chosen for delivery. The adapted plan was used for all five fractions and met all critical OAR constraints while maintaining target coverage. The use of the scheduled plan would have resulted in stomach and/or esophagus constraint violations on all five fractions. This resulted in reduced EQD2 doses of 6.4 and 12.3 Gy for the esophagus and stomach, respectively. We report the successful treatment of a patient undergoing tri-site SBRT re-irradiation with concurrent CT-guided adaptive radiotherapy to a gsLN. The adaptive treatment allowed us to meet critical OAR constraints while maintaining target coverage. Few studies have described the use of CT-guided adaptive radiotherapy in re-irradiation cases, and the potential benefit for these complex cases is evident.

Detoxification of ars genotypes by arsenite-oxidizing bacteria through arsenic biotransformation.

The detoxification process of transforming arsenite (As(III)) to arsenate (As(V)) through bacterial oxidation presents a potent approach for bioremediation of arsenic-polluted soils in abandoned mines. In this study, twelve indigenous arsenic-oxidizing bacteria (AOB) were isolated from arsenic-contaminated soils. Among these, Paenibacillus xylanexedens EBC-SK As2 (MF928871) and Ochrobactrum anthropi EBC-SK As11 (MF928880) were identified as the most effective arsenic-oxidizing isolates. Evaluations for bacterial arsenic resistance demonstrated that P. xylanexedens EBC-SK As2 (MF928871) could resist As(III) up to 40 mM, while O. anthropi EBC-SK As11 (MF928880) could resist As(III) up to 25 mM. From these bacterial strains, genotypes of arsenic resistance system (ars) were detected, encompassing ars leader genes (arsR and arsD), membrane genes (arsB and arsJ), and aox genes known to be crucial for arsenic detoxification. These ars genotypes in the isolated AOBs might play an instrumental role in arsenic-contaminated soils with potential to reduce arsenic contamination.

A stochastic photo-responsive memristive neuron for an in-sensor visual system based on a restricted Boltzmann machine.

In-sensor computing has gained attention as a solution to overcome the von Neumann computing bottlenecks inherent in conventional sensory systems. This attention is due to the ability of sensor elements to directly extract meaningful information from external signals, thereby simplifying complex data. The advantage of in-sensor computing can be maximized with the sampling principle of a restricted Boltzmann machine (RBM) to extract significant features. In this study, a stochastic photo-responsive neuron is developed using a TiN/In-Ga-Zn-O/TiN optoelectronic memristor and an Ag/HfO2/Pt threshold-switching memristor, which can be configured as an input neuron in an in-sensor RBM. It demonstrates a sigmoidal switching probability depending on light intensity. The stochastic properties allow for the simultaneous exploration of various neuron states within the network, making identifying optimal features in complex images easier. Based on semi-empirical simulations, high recognition accuracies of 90.9% and 95.5% are achieved using handwritten digit and face image datasets, respectively. In addition, the in-sensor RBM effectively reconstructs abnormal face images, indicating that integrating in-sensor computing with probabilistic neural networks can lead to reliable and efficient image recognition under unpredictable real-world conditions.

Correlation between fetal subcutaneous fat thickness and insulin resistance through cord blood analysis immediately after delivery.

OBJECTIVES: This study aimed to determine whether fetal subcutaneous tissue (SCT) thickness, measured using ultrasound immediately before and after delivery, can reflect changes in glucose metabolism immediately after delivery. We also evaluated the impact of insulin resistance changes during pregnancy by comparing pregnant women with well-controlled gestational diabetes mellitus (GDM) and those with normal glucose metabolism. STUDY DESIGN: The study participants were 117 pregnant women, including 97 controls and 20 patients with GDM who visited our obstetric clinic between February and December 2022. The participants were scheduled for cesarean delivery at a gestational age of ≥37 weeks. SCT thickness before delivery was measured using ultrasound and within 48 h after delivery using Holtain calipers. The glucose and insulin concentrations were quantified from cord blood collected immediately after delivery. Based on these results, a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was performed to assess insulin resistance. Independent t-test or Wilcoxon rank-sum test for continuous variables and Fisher's exact test for categorical variables were used to compare the various parameters. Correlations among the variables in each group were assessed by calculating the correlation coefficient (Pearson's correlation). RESULTS: SCT thickness measured using ultrasound and calipers demonstrated a strong correlation where pregnant women with GDM exhibited thicker fetal SCT and neonate skinfolds than in those without GDM. Glucose and insulin levels in the cord blood were significantly elevated (p < 0.05) in the gestational diabetic group, along with remarkable differences (p < 0.001) in HOMA-IR. These variables indicated a higher prevalence of glucose intolerance in the neonates of mothers with GDM. In pregnant women with GDM, there was a statistically significant correlation between fetal abdominal SCT thickness and glucose levels (r = 0.64, p < 0.01) and HOMA-IR (r = 0.48, p < 0.05). CONCLUSIONS: Measuring the subcutaneous fat thickness of the fetus shortly before delivery is beneficial for predicting insulin resistance in neonates. This is considered particularly useful for women with effectively managed GDM, where the presence of conditions such as macrosomia may not be pronounced.

Therapeutic Performance of Needle Injection Versus Needle-Free Jet Injector System for Polynucleotide Filler in Skin Rejuvenation.

BACKGROUND: Polynucleotide (PN) filler often causes pain and can lead to delivery inaccuracies when applied via intradermal injection using a traditional needle. AIMS: To evaluate the efficacy of treatment and the pain during the procedure using conventional needle injection versus a needle-free jet system for intradermal PN filler application. METHODS: In this split-face clinical trial, 10 Korean subjects were enrolled. Each subject received an intradermal injection of PN filler on one side of the face and a needle-free jet injection using CureJet on the other side. Assessments included global and 3D skin imaging at each visit. Pain intensity was evaluated using visual analogue scale (VAS) scores during the injection. Additionally, patient satisfaction and adverse events were documented. RESULTS: Findings revealed that Global Aesthetic Improvement Scale scores and patient satisfaction were significantly higher with the CureJet compared to the needle injection method. VAS scores were notably lower on the CureJet side. Improvements in both pore and wrinkle indices were observed from baseline, with a more pronounced improvement rate on the CureJet side compared to the needle injection side. CONCLUSIONS: Needle-free injection of PN for aging skin was found to be effective in enhancing pore and wrinkle improvement, while reducing associated discomfort.

A pilot study of skin barrier function in patients with systemic sclerosis and primary Sjögren's syndrome.

Objective: Although the close interactions between the epidermis and dermis of the skin have been widely explored, the skin barrier functions of the stratum corneum (SC) in patients with systemic sclerosis (SSc) and primary Sjögren's syndrome (pSS) are not well known. We aimed to investigate the biophysical characteristics of the skin, including transepidermal water loss (TEWL), the SC water content, erythema, and the melanin index, in patients with SSc and pSS. Methods: This case-control study included 34 patients with SSc, 31 patients with pSS, and 25 healthy controls. All parameters were measured on the extensor surface of the forearm and compared between patients and healthy controls. In patients with SSc, we performed subgroup analyses by disease subtype (diffuse and limited cutaneous SSc), the modified Rodnan skin sclerosis score (>6 or ≤6), and comorbid secondary SS status. In patients with pSS, subgroup analyses were performed by anti-Ro/SSA antibody status and the findings of salivary gland ultrasound. Results: No statistically significant differences were observed in TEWL or skin hydration between patients with SSc and pSS and healthy controls. In the pSS group, only the erythema index was significantly increased compared to the control group. In subgroup analyses, no significant differences were observed in the extent of TEWL or skin hydration by disease subtype, severity, autoantibody profile, or comorbidities. Conclusion: Patients with SSc or pSS did not exhibit specific impairments of skin barrier function or skin hydration. Further studies with larger sample sizes and age-matched controls are required.

Paired Transcriptional Analysis of Periodontitis and Peri-Implantitis within same host: a Pilot study.

BACKGROUND: Peri-implantitis, a plaque-associated pathological condition, has been on the rise with the increasing prevalence of dental implants. Despite its similarities to periodontitis, peri-implantitis is difficult to control completely and has high relapse rates. This has sparked interest in exploring the pathogenic differences between the two conditions. METHODS: This cross-sectional study involved 10 participants to concurrently examine periodontitis and peri-implantitis within the same patients, thereby minimizing inter-individual variation. Gingival tissue samples were collected from each participant, comprising 10 periodontitis and 10 peri-implantitis tissues, and RNAs were extracted. Using RNA sequencing and bioinformatics analysis, we investigated complex gene interactions, immune responses, and the role of the extracellular matrix in both conditions. We identified hub genes in each enhanced Protein-Protein Interaction network, providing crucial insights into these diseases' pathogenesis. RESULTS: Our findings highlighted the potential involvement of activated fibroblasts in the pathogenesis of peri-implantitis, identifying three marker genes (ACTA2, FAP, and PDGFRß) overexpressed in peri-implantitis, thus highlighting their potential as disease-specific biomarkers. CONCLUSIONS: Our study uncovered a novel connection between peri-implantitis and activated fibroblasts, examining specific markers and microbial differences between periodontitis and peri-implantitis. These insights improve our understanding of peri-implantitis pathogenesis, encouraging future research for better management and prevention strategies. CLINICAL SIGNIFICANCE: This study identifies key insights into the pathogenesis of peri-implantitis compared to periodontitis. These findings promise to advance clinical approaches for better managing and preventing peri-implantitis, addressing its complexities and high relapse rates effectively.

An integrative single-cell atlas for exploring the cellular and temporal specificity of genes related to neurological disorders during human brain development.

Single-cell technologies have enhanced comprehensive knowledge regarding the human brain by facilitating an extensive transcriptomic census across diverse brain regions. Nevertheless, understanding the cellular and temporal specificity of neurological disorders remains ambiguous due to developmental variations. To address this gap, we illustrated the dynamics of disorder risk gene expression under development by integrating multiple single-cell RNA sequencing datasets. We constructed a comprehensive single-cell atlas of the developing human brain, encompassing 393,060 single cells across diverse developmental stages. Temporal analysis revealed the distinct expression patterns of disorder risk genes, including those associated with autism, highlighting their temporal regulation in different neuronal and glial lineages. We identified distinct neuronal lineages that diverged across developmental stages, each exhibiting temporal-specific expression patterns of disorder-related genes. Lineages of nonneuronal cells determined by molecular profiles also showed temporal-specific expression, indicating a link between cellular maturation and the risk of disorder. Furthermore, we explored the regulatory mechanisms involved in early brain development, revealing enriched patterns of fetal cell types associated with neuronal disorders indicative of the prenatal stage's influence on disease determination. Our findings facilitate unbiased comparisons of cell type‒disorder associations and provide insight into dynamic alterations in risk genes during development, paving the way for a deeper understanding of neurological disorders.

Comparison of Synergistic Sedation with Midazolam and Propofol Versus Midazolam and Pethidine in Colonoscopies: A Prospective, Randomized Controlled Study.

Colonoscopy is a key procedure for the early detection of colorectal cancer. Despite its importance, the discomfort associated with colonoscopy often requires sedation, and the ideal sedation regimen remains to be determined. In this prospective randomized controlled trial, patients scheduled for colonoscopy were randomly assigned to two different sedation protocols. Group A received a combination of midazolam and propofol, while group B was given midazolam and pethidine. The study analyzed data from 51 patients, with 23 in group A and 28 in group B. The incidence of adverse events was similar across both groups. Additionally, no significant differences were observed in cecal intubation times or total procedure durations. Notably, group A had a lower frequency of required postural changes (1.0±.7 vs. 1.5±0.7, p=0.02) and a reduced rate of manual compression (52.2% vs. 82.1%, p=0.02). There were no significant differences between the groups regarding subjective pain or overall satisfaction. Both sedation regimens were found to be safe and effective. The midazolam and propofol combination was associated with a smoother procedure, evidenced by fewer postural adjustments and less manual compression needed during colonoscopy.

Habitat Loss in the IUCN Extent: Climate Change-Induced Threat on the Red Goral (Naemorhedus baileyi) in the Temperate Mountains of South Asia.

Climate change has severely impacted many species, causing rapid declines or extinctions within their essential ecological niches. This deterioration is expected to worsen, particularly in remote high-altitude regions like the Himalayas, which are home to diverse flora and fauna, including many mountainous ungulates. Unfortunately, many of these species lack adaptive strategies to cope with novel climatic conditions. The Red Goral (Naemorhedus baileyi) is a cliff-dwelling species classified as "Vulnerable" by the IUCN due to its small population and restricted range extent. This species has the most restricted range of all goral species, residing in the temperate mountains of northeastern India, northern Myanmar, and China. Given its restricted range and small population, this species is highly threatened by climate change and habitat disruptions, making habitat mapping and modeling crucial for effective conservation. This study employs an ensemble approach (BRT, GLM, MARS, and MaxEnt) in species distribution modeling to assess the distribution, habitat suitability, and connectivity of this species, addressing critical gaps in its understanding. The findings reveal deeply concerning trends, as the model identified only 21,363 km2 (13.01%) of the total IUCN extent as suitable habitat under current conditions. This limited extent is alarming, as it leaves the species with very little refuge to thrive. Furthermore, this situation is compounded by the fact that only around 22.29% of this identified suitable habitat falls within protected areas (PAs), further constraining the species' ability to survive in a protected landscape. The future projections paint even degraded scenarios, with a predicted decline of over 34% and excessive fragmentation in suitable habitat extent. In addition, the present study identifies precipitation seasonality and elevation as the primary contributing predictors to the distribution of this species. Furthermore, the study identifies nine designated transboundary PAs within the IUCN extent of the Red Goral and the connectivity among them to highlight the crucial role in supporting the species' survival over time. Moreover, the Dibang Wildlife Sanctuary (DWLS) and Hkakaborazi National Park are revealed as the PAs with the largest extent of suitable habitat in the present scenario. Furthermore, the highest mean connectivity was found between DWLS and Mehao Wildlife Sanctuary (0.0583), while the lowest connectivity was observed between Kamlang Wildlife Sanctuary and Namdapha National Park (0.0172). The study also suggests strategic management planning that is a vital foundation for future research and conservation initiatives, aiming to ensure the long-term survival of the species in its natural habitat.