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1.
J Psychosom Res ; 187: 111936, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39306900

ABSTRACT

OBJECTIVE: Though the association between peripheral neurophysiological biomarkers and psychological conditions is widely discussed, there is still limited evidence about the ability of peripheral biomarkers to predict psychological outcomes, especially among geriatric populations. METHODS: The study is designed as a prospective cohort study. We collected information from participants aged over 55 years. The participants were evaluated at the start of the study (T0) and 6-9 months later (T1). Information about demographic profiles, peripheral neurophysiological biomarker recordings (including heart rate variability, finger temperature, skin conductance, and electromyogram), and psychological measurements (including Brief Symptom Rating Scale-5, Chinese Happiness Inventory, and Short Portable Mental Status Questionnaire) were collected at T0. At T1, participants reported self-rated questionnaires for psychological outcomes (Patient Health Questionnaire-15, health anxiety questionnaire, Beck Depression Inventory-II, and Beck Anxiety Inventory) and were evaluated with Mini-Mental State Examination by the staff. The association between the peripheral biomarkers and psychological outcomes was evaluated via multiple regression models. RESULTS: A total of 385 participants were included in the study and the average age was 74.49 ± 7.34 years. Both stepwise multiple linear and logistic models showed a significant association between decreased skin conductance and increased/presence of depression at T1. The receiver operating characteristic (ROC) curve analysis of skin conductance for depression was fair (area under curve = 0.812). CONCLUSIONS: The ability of skin conductance to predict depression among geriatric populations may facilitate the detection of geriatric depression and future research on the pathophysiology.

2.
Nano Lett ; 24(38): 11847-11852, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39264273

ABSTRACT

The pseudomagnetic field effect may offer unique opportunities for the emergence of intriguing phenomena. To date, investigations into pseudomagnetic field effects on phonons have been limited to sound waves in metamaterials. The revelation of this exotic effect on the atomic vibration of natural materials remains elusive. Our simulations of twisted graphene nanoribbons reveal well-defined Landau spectra and sublattice polarization of phonon states, mimicking the behavior of Dirac Fermions in magnetic fields. Both valley-specified helical edge currents and snake orbits are obtained. Analysis of dynamics indicates that phonon Landau states have extended lifetimes, which are crucial for the realization of Landau-level lasing. Our findings demonstrate the occurrence of the phonon pseudomagnetic field effect in natural materials, which has important implications for the mechanical tuning of phonon quantum states at the atomic scale.

3.
Medicine (Baltimore) ; 103(36): e39088, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39252257

ABSTRACT

RATIONALE: Approximately one-fifth ischemic stroke are attributed to cardioembolism. Patients with cardioembolic stroke often develop a more severe disability and a higher risk of stroke recurrence. Cardiac myxoma, although uncommon, can serve as a potentially curable cause of acute embolic strokes. PATIENT CONCERNS: A 55-year-old male patient presented to the emergency department with acute vertigo and unsteady gait, accompanied by left upper limb numbness. Concurrently, purple-like lesions on the left hand were noticed. DIAGNOSES: Brain magnetic resonance imaging showed multiple infarctions in the posterior circulation. Additionally, skin examination showed Janeway lesions, Osler nodes and splinter hemorrhages. There was no evidence of systemic infection. Subsequently, transthoracic echocardiogram revealed a left atrial myxoma. INTERVENTION: Early surgical resection of cardiac myxoma was performed. OUTCOMES: The patient recovered well from the surgery. No recurrent embolic event was reported at 3-month postoperatively. LESSONS: Clinicians should be vigilant for skin manifestations of cardiac embolism. In patients with acute ischemic strokes, the presence of cutaneous embolic phenomena could serve as a warning sign of cardioembolism.


Subject(s)
Heart Atria , Heart Neoplasms , Ischemic Stroke , Myxoma , Humans , Male , Myxoma/complications , Myxoma/diagnosis , Myxoma/surgery , Middle Aged , Heart Neoplasms/complications , Heart Neoplasms/diagnosis , Heart Neoplasms/surgery , Ischemic Stroke/etiology , Heart Atria/diagnostic imaging , Endocarditis/complications , Endocarditis/diagnosis , Echocardiography
4.
ACS Nano ; 18(37): 25478-25488, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39236319

ABSTRACT

SnSe, an environmental-friendly group-IV monochalcogenide semiconductor, demonstrates outstanding performance in various applications ranging from thermoelectric devices to solar energy harvesting. Its ultrathin films show promise in the fabrication of ferroelectric nonvolatile devices. However, the microscopic identification and manipulation of point defects in ultrathin SnSe single crystalline films, which significantly impact their electronic structure, have been inadequately studied. This study presents a comprehensive investigation of point defects in monolayer SnSe films grown via molecular beam epitaxy. By combining scanning tunneling microscopy (STM) characterization with first-principles calculations, we identified four types of atomic/molecular vacancies, four types of atomic substitutions, and three types of extrinsic defects. Notably, we have demonstrated the ability to convert a substitutional defect into a vacancy and to reposition an adsorbate by manipulating a single atom or molecule using an STM tip. We have also analyzed the local atomic displacement induced by the vacancies. This work provides a solid foundation for engineering the electronic structure of future SnSe-based nanodevices.

5.
Aging Clin Exp Res ; 36(1): 193, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39311977

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is a significant health concern, particularly among older adults. Outcomes between laparoscopic and robot-assisted surgeries for right-sided colon cancers in the oldest old population have yet to be evaluated despite increased use of these surgeries. AIM: This study aimed to compare clinical outcomes after robot-assisted right hemicolectomy (RARH) versus laparoscopic right hemicolectomy (LRH) in octogenarian and nonagenarian patients. METHODS: This population-based, retrospective and observational study analyzed the data of adults ≥ 80 years old diagnosed with right-side colon cancer who received RARH or LRH. All data were extracted from the US National Inpatient Sample (NIS) database 2005-2018. Associations between type of surgery and in-hospital outcomes were determined using univariate and multivariable logistic regression and linear regression analysis. RESULTS: Data of 7,550 patients (representing 37,126 hospitalized patients in the U.S.) were analyzed. Mean age of the study population was 84.8 years, 61.4% were females, and 79.1% were non-smokers. After adjusting for relevant confounders, regression analysis showed that patients undergoing RARH had a significantly shorter LOS (adjusted Beta (aBeta), -0.24, 95% CI: -0.32, -0.15) but greater total hospital costs (aBeta, 26.54, 95% CI: 24.64, 28.44) than patients undergoing LRH. No significant differences in mortality, perioperative complications, and risk of unfavorable discharge were observed between the two procedures (p > 0.05). Stratified analyses by frailty status revealed consistent results. CONCLUSIONS: RARH is associated with a significantly shorter LOS but higher total hospital costs than LRH among octogenarians and nonagenarians. Other short-term outcomes for this population are similar between the two procedures, including in-hospital mortality, perioperative complications, and unfavorable discharge. These findings also apply to frail patients.


Subject(s)
Colectomy , Laparoscopy , Robotic Surgical Procedures , Humans , Female , Male , Colectomy/methods , Laparoscopy/methods , Laparoscopy/statistics & numerical data , Aged, 80 and over , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/statistics & numerical data , Retrospective Studies , United States/epidemiology , Inpatients , Length of Stay , Treatment Outcome , Postoperative Complications/epidemiology , Colonic Neoplasms/surgery , Colonic Neoplasms/mortality
6.
Noncoding RNA Res ; 9(4): 1351-1362, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39247145

ABSTRACT

Prostate cancer (PCa) has the highest frequency of diagnosis among solid tumors and ranks second as the primary cause of cancer-related deaths. Non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs and circular RNAs, frequently exhibit dysregulation and substantially impact the biological behavior of PCa. Compared with circulating ncRNAs, ncRNAs loaded into exosomes are more stable because of protection by the lipid bilayer. Furthermore, exosomal ncRNAs facilitate the intercellular transfer of molecules and information. Increasing evidence suggests that exosomal ncRNAs hold promising potential in the progression, diagnosis and prognosis of PCa. This review aims to discuss the functions of exosomal ncRNAs in PCa, evaluate their possible applications as clinical biomarkers and therapeutic targets, and provide a comprehensive overview of the ncRNAs regulatory network in PCa. We also identified ncRNAs that can be utilized as biomarkers for diagnosis, staging, grading and prognosis assessment in PCa. This review offers researchers a fresh perspective on the functions of exosomal ncRNAs in PCa and provides additional options for its diagnosis, progression monitoring, and prognostic prediction.

8.
Article in English | MEDLINE | ID: mdl-39209206

ABSTRACT

BACKGROUND & AIMS: A functional cure is an essential endpoint in the management of patients with chronic hepatitis B virus (HBV) infection. We evaluated the cumulative probability and predictors of functional cure in patients with chronic HBV infection after hepatitis B e antigen (HBeAg) seroconversion. METHODS: We retrospectively analyzed 413 (249 males and 164 females) initially HBeAg-positive chronic HBV-infected patients who were followed up for a mean of 26.36 ± 0.53 years. All underwent HBeAg seroconversion during follow-up. A functional cure was defined as durable HBsAg and HBV DNA loss without antiviral treatment for more than 24 weeks. RESULTS: After 10,888 person-years of follow-up, the cumulative probability of functional cure was 14.53% (n = 60). There were 24 (40%) subjects with functional cure after antiviral therapy. The annual functional cure rate was 0.55% per person-year, and increased to 0.96% per person-year after HBeAg seroconversion. In subjects with functional cure, the HBsAg and HBV DNA titers after HBeAg seroconversion were positively correlated with the time to functional cure (P < .001 and < .001, respectively). Multivariate Cox proportional hazards analysis of the cohort revealed that HBeAg seroconversion at <18 years of age, high-genetic-barrier nucleos(t)ide analogue(s) therapy before HBeAg seroconversion, and a serum HBsAg titer <1000 IU/mL at 18 months after HBeAg seroconversion were significant predictors of functional cure (P < .001, .001, and .001, respectively). CONCLUSIONS: In a cohort of chronic HBV-infected patients with long-term follow-up, HBeAg seroconversion in childhood, high-genetic-barrier nucleos(t)ide analogue(s) therapy, and low HBsAg titers after HBeAg seroconversion were significant predictors of functional cure.

9.
bioRxiv ; 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39185152

ABSTRACT

Single-cell transcriptomics is valuable for uncovering individual cell properties, particularly in highly heterogeneous systems. However, this technique often results in the analysis of many well-characterized cells, increasing costs and diluting rare cell populations. To address this, we developed PURE-seq (PIP-seq for Rare-cell Enrichment and Sequencing) for scalable sequencing of rare cells. PURE-seq allows direct cell loading from FACS into PIP-seq reactions, minimizing handling and reducing cell loss. PURE-seq reliably captures rare cells, with 60 minutes of sorting capturing tens of cells at a rarity of 1 in 1,000,000. Using PURE-seq, we investigated murine long-term hematopoietic stem cells and their transcriptomes in the context of hematopoietic aging, identifying Egr1 as a potential master regulator of hematopoiesis in the aging context. PURE-seq offers an accessible and reliable method for isolating and sequencing cells that are currently too rare to capture successfully with existing methods.

10.
Cell Death Dis ; 15(8): 599, 2024 Aug 18.
Article in English | MEDLINE | ID: mdl-39155279

ABSTRACT

Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide, exhibiting unique regional prevalence. Despite advancements in diagnostics and therapy, the 5-year survival rate for patients has seen limited improvement. A deeper understanding of OSCC pathogenesis, especially its molecular underpinnings, is essential for improving detection, prevention, and treatment. In this context, noncoding RNAs, such as circular RNAs (circRNAs), have gained recognition as crucial regulators and potential biomarkers in OSCC progression. Our study highlights the discovery of previously uncharacterized circRNAs, including a SNX5 gene-derived circRNA, circSNX5, through deep sequencing of OSCC patient tissue transcriptomes. We established circSNX5's tumor-specific expression and its strong correlation with patient survival using structure-specific and quantitative PCR analyses. In vitro and in vivo experiments underscored circSNX5 RNA's regulatory role in cancer growth and metastasis. Further, our omics profiling and functional assays revealed that ADAM10 is a critical effector in circSNX5-mediated cancer progression, with circSNX5 maintaining ADAM10 expression by sponging miR-323. This novel circRNA-miRNA-mRNA regulatory axis significantly contributes to oral cancer progression and malignancy. Moreover, we discovered that circSNX5 RNA is produced via noncanonical sequential back-splicing of pre-mRNA, a process negatively regulated by the RNA-binding protein STAU1. This finding adds a new dimension to our understanding of exonic circRNA biogenesis in the eukaryotic transcriptome. Collectively, our findings offer a detailed mechanistic dissection and functional interpretation of a novel circRNA, shedding light on the role of the noncoding transcriptome in cancer biology and potentially paving the way for innovative therapeutic strategies.


Subject(s)
Mouth Neoplasms , RNA, Circular , Sorting Nexins , Humans , RNA, Circular/genetics , RNA, Circular/metabolism , Sorting Nexins/metabolism , Sorting Nexins/genetics , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Animals , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell Proliferation/genetics , Mice , Mice, Nude , MicroRNAs/metabolism , MicroRNAs/genetics , Male , Female , ADAM10 Protein/metabolism , ADAM10 Protein/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism
11.
Article in English | MEDLINE | ID: mdl-39182723

ABSTRACT

BACKGROUND: Intermittent theta burst stimulation (iTBS) of the dorsolateral prefrontal cortex (DLPFC) is widely applied as therapeutic intervention in mental health, however understanding of its mechanisms is still incomplete. Prior MRI studies have mainly used offline iTBS or short sequences in concurrent TMS-fMRI. This study investigated a full 600 stimuli iTBS protocol using interleaved TMS-fMRI in comparison with two control conditions in healthy subjects. METHODS: In a crossover design, 18 participants underwent three sessions of interleaved iTBS-fMRI: 1) left DLPFC at 40% resting motor threshold (rMT) intensity, 2) left DLPFC at 80% rMT intensity, and 3) left primary motor cortex (M1) at 80% rMT intensity. We compared immediate blood-oxygen-level-dependent (BOLD) responses during interleaved iTBS-fMRI across these conditions including correlations between individual fMRI BOLD activation and iTBS induced electric field (E-field) strength at the target sites. RESULTS: Whole-brain analysis showed increased activation in several regions following iTBS. Specifically, left DLPFC, as well as bilateral M1, anterior cingulate cortex, and insula showed increased activation during 80% rMT left DLPFC stimulation. Increased BOLD activity in the left DLPFC was not observed with 40% rMT left DLPFC stimulation nor left M1 80% rMT iTBS, whereas activation in other regions was found to overlap between conditions. Of note, BOLD activation and E-field intensities were only correlated for M1 stimulation, but not for the DLPFC conditions. CONCLUSIONS: The study showed dosage and target specific BOLD activation during interleaved TMS-fMRI with 600 stimuli iTBS in healthy subjects. Future studies may use our approach for demonstrating target engagement.

12.
bioRxiv ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39211079

ABSTRACT

Monocyte-derived macrophages recruited to injured tissues induce a maladaptive fibrotic response characterized by excessive production of collagen by local fibroblasts. Macrophages initiate this programming via paracrine factors, but it is unknown whether reciprocal responses from fibroblasts enhance profibrotic polarization of macrophages. We identify macrophage-fibroblast crosstalk necessary for injury-associated fibrosis, in which macrophages induced interleukin 6 ( IL-6 ) expression in fibroblasts via purinergic receptor P2rx4 signaling, and IL-6, in turn, induced arginase 1 ( Arg1 ) expression in macrophages. Arg1 contributed to fibrotic responses by metabolizing arginine to ornithine, which fibroblasts used as a substrate to synthesize proline, a uniquely abundant constituent of collagen. Imaging of idiopathic pulmonary fibrosis (IPF) lung samples confirmed expression of ARG1 in myeloid cells, and arginase inhibition suppressed collagen expression in cultured precision-cut IPF lung slices. Taken together, we define a circuit between macrophages and fibroblasts that facilitates cross-feeding metabolism necessary for injury-associated fibrosis.

13.
Int J Med Inform ; 191: 105555, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39089210

ABSTRACT

OBJECTIVE: Symptoms are significant kind of phenotypes for managing and controlling of the burst of acute infectious diseases, such as COVID-19. Although patterns of symptom clusters and time series have been considered the high potential prediction factors for the prognosis of patients, the elaborated subtypes and their progression patterns based on symptom phenotypes related to the prognosis of COVID-19 patients still need be detected. This study aims to investigate patient subtypes and their progression patterns with distinct features of outcome and prognosis. METHODS: This study included a total of 14,139 longitudinal electronic medical records (EMRs) obtained from four hospitals in Hubei Province, China, involving 2,683 individuals in the early stage of COVID-19 pandemic. A deep representation learning model was developed to help acquire the symptom profiles of patients. K-means clustering algorithm is used to divide them into distinct subtypes. Subsequently, symptom progression patterns were identified by considering the subtypes associated with patients upon admission and discharge. Furthermore, we used Fisher's test to identify significant clinical entities for each subtype. RESULTS: Three distinct patient subtypes exhibiting specific symptoms and prognosis have been identified. Particularly, Subtype 0 includes 44.2% of the whole and is characterized by poor appetite, fatigue and sleep disorders; Subtype 1 includes 25.6% cases and is characterized by confusion, cough with bloody sputum, encopresis and urinary incontinence; Subtype 2 includes 30.2% cases and is characterized by dry cough and rhinorrhea. These three subtypes demonstrate significant disparities in prognosis, with the mortality rates of 4.72%, 8.59%, and 0.25% respectively. Furthermore, symptom cluster progression patterns showed that patients with Subtype 0 who manifest dark yellow urine, chest pain, etc. in the admission stage exhibit an elevated risk of transforming into the more severe subtypes with poor outcome, whereas those presenting with nausea and vomiting tend to incline towards entering the milder subtype. CONCLUSION: This study has proposed a clinical meaningful approach by utilizing the deep representation learning and real-world EMR data containing symptom phenotypes to identify the COVID-19 subtypes and their progression patterns. The results would be potentially useful to help improve the precise stratification and management of acute infectious diseases.


Subject(s)
COVID-19 , Deep Learning , Disease Progression , Electronic Health Records , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/diagnosis , Electronic Health Records/statistics & numerical data , Prognosis , Female , Male , Middle Aged , China/epidemiology , Adult , Aged
14.
Phys Rev Lett ; 133(3): 036204, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39094154

ABSTRACT

Solving the Hamiltonian of a system yields the energy dispersion and eigenstates. The geometric phase of the eigenstates generates many novel effects and potential applications. However, the geometric properties of the energy dispersion go unheeded. Here, we provide geometric insight into energy dispersion and introduce a geometric amplitude, namely, the geometric density of states (GDOS) determined by the Riemann curvature of the constant-energy contour. The geometric amplitude should accompany various local responses, which are generally formulated by the real-space Green's function. Under the stationary phase approximation, the GDOS simplifies the Green's function into its ultimate form. In particular, the amplitude factor embodies the spinor phase information of the eigenstates, favoring the extraction of the spin texture for topological surface states under an in-plane magnetic field through spin-polarized STM measurements. This work opens a new avenue for exploring the geometric properties of electronic structures and excavates the unexplored potential of spin-polarized STM measurements to probe the spinor phase information of eigenstates from their amplitudes.

15.
Clin Otolaryngol ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39115223

ABSTRACT

BACKGROUND: This study was designed to evaluate the diagnostic efficacy of the minimum fascia-tumour distance (MFTD) in distinguishing deep-lobe benign parotid tumours from superficial-lobe tumours through both an original study and a meta-analysis. METHODS: In this study, we performed a retrospective analysis of data from 91 patients who had been diagnosed with benign parotid tumours. The MFTD values were sourced from preoperative ultrasound examinations. The locations of these tumours were confirmed through surgical findings. We assessed the diagnostic accuracy of MFTD by utilising receiver operating characteristic (ROC) curves. Additionally, we conducted a systematic review of the pertinent literature and performed a diagnostic meta-analysis to ascertain the overall diagnostic efficacy of MFTD in identifying benign parotid tumours. RESULTS: Patients with tumours in the deep lobe had a significantly greater MFTD than patients with tumours in the superficial lobe. Using a cutoff value of 3.50 mm for MFTD, we found an AUC of 0.93, a sensitivity of 81.8%, and a specificity of 98.8%. Our meta-analysis included seven studies covering a total of 1689 tumours. The pooled values for sensitivity, specificity, and diagnostic odds ratio (OR) of MFTD were 81.0%, 89.0%, and 32.2, respectively. The AUC of the summarised ROC curve of MFTD was 0.90. CONCLUSION: The MFTD demonstrated reliable diagnostic accuracy in identifying deep-lobe benign parotid tumours and may be incorporated into standard evaluations before parotidectomy.

16.
Res Sq ; 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39184105

ABSTRACT

Single-cell transcriptomics is valuable for uncovering individual cell properties, particularly in highly heterogeneous systems. However, this technique often results in the analysis of many well-characterized cells, increasing costs and diluting rare cell populations. To address this, we developed PURE-seq (PIP-seq for Rare-cell Enrichment and Sequencing) for scalable sequencing of rare cells. PURE-seq allows direct cell loading from FACS into PIP-seq reactions, minimizing handling and reducing cell loss. PURE-seq reliably captures rare cells, with 60 minutes of sorting capturing tens of cells at a rarity of 1 in 1,000,000. Using PURE-seq, we investigated murine long-term hematopoietic stem cells and their transcriptomes in the context of hematopoietic aging, identifying Egr1 as a potential master regulator of hematopoiesis in the aging context. PURE-seq offers an accessible and reliable method for isolating and sequencing cells that are currently too rare to capture successfully with existing methods.

17.
Int J Mol Sci ; 25(16)2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39201722

ABSTRACT

Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder among women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The pathogenesis of PCOS involves a complex interplay of genetic and environmental factors, including insulin resistance (IR) and resultant hyperinsulinemia. Insulin receptors, primarily in skeletal muscle, liver, and adipose tissue, activate downstream signaling pathways like PI3K-AKT and MAPK-ERK upon binding. These pathways regulate glucose uptake, storage, and lipid metabolism. Genome-wide association studies (GWASs) have identified several candidate genes related to steroidogenesis and insulin signaling. Environmental factors such as endocrine-disrupting chemicals and lifestyle choices also exacerbate PCOS traits. Other than lifestyle modification and surgical intervention, management strategies for PCOS can be achieved by using pharmacological treatments like antiandrogens, metformin, thiazolidinediones, aromatase inhibitor, and ovulation drugs to improve insulin sensitivity and ovulatory function, as well as combined oral contraceptives with or without cyproterone to resume menstrual regularity. Despite the complex pathophysiology and significant economic burden of PCOS, a comprehensive understanding of its molecular and cellular mechanisms is crucial for developing effective public health policies and treatment strategies. Nevertheless, many unknown aspects of PCOS, including detailed mechanisms of actions, along with the safety and effectiveness for the treatment, warrant further investigation.


Subject(s)
Insulin Resistance , Polycystic Ovary Syndrome , Polycystic Ovary Syndrome/therapy , Polycystic Ovary Syndrome/metabolism , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/etiology , Humans , Female , Signal Transduction/drug effects , Animals
18.
JHEP Rep ; 6(7): 101090, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39006502

ABSTRACT

Background & Aims: The gut microbiome plays an important role in liver diseases, but its specific impact on biliary atresia (BA) remains to be explored. We aimed to investigate the microbial signature in the early life of patients with BA and to analyze its influence on long-term outcomes. Methods: Fecal samples (n = 42) were collected from infants with BA before and after Kasai portoenterostomy (KPE). The stool microbiota was analyzed using 16S rRNA next-generation sequencing and compared with that of age-matched healthy controls (HCs). Shotgun metagenomic sequencing analysis was employed to confirm the bacterial composition in 10 fecal samples before KPE. The correlation of the microbiome signature with liver function and long-term outcomes was assessed. Results: In the 16S rRNA next-generation sequencing analysis of fecal microbiota, the alpha and beta diversity analyses revealed significant differences between HCs and patients with BA before and after KPE. The difference in microbial composition analyzed by linear discriminant analysis and random forest classification revealed that the abundance of Bifidobacterium longum (B. longum) was significantly lower in patients before and after KPE than in HCs. The abundance of B. longum was negatively correlated with the gamma-glutamyltransferase level after KPE (p <0.05). Patients with early detectable B. longum had significantly lower total and direct bilirubin 3 months after KPE (p <0.005) and had a significantly lower liver transplantation rate (hazard ratio: 0.16, 95% CI 0.03-0.83, p = 0.029). Shotgun metagenomic sequencing also revealed that patients with BA and detectable B. longum had reduced total and direct bilirubin after KPE. Conclusion: The gut microbiome of patients with BA differed from that of HCs, with a notable abundance of B. longum in early infancy correlating with better long-term outcomes. Impact and implications: Bifidobacterium longum (B. longum) is a beneficial bacterium commonly found in the human gut. It has been studied for its potential impacts on various health conditions. In patients with biliary atresia, we found that a greater abundance of B. longum in the fecal microbiome is associated with improved clinical outcomes. This suggests that early colonization and increasing B. longum levels in the gut could be a therapeutic strategy to improve the prognosis of patients with biliary atresia.

19.
Biology (Basel) ; 13(7)2024 Jul 06.
Article in English | MEDLINE | ID: mdl-39056697

ABSTRACT

Background: While frontotemporal involvement is increasingly recognized in Amyotrophic lateral sclerosis (ALS), the degeneration of limbic networks remains poorly characterized, despite growing evidence of amnestic deficits, impaired emotional processing and deficits in social cognition. Methods: A prospective neuroimaging study was conducted with 204 individuals with ALS and 111 healthy controls. Patients were stratified for hexanucleotide expansion status in C9orf72. A deep-learning-based segmentation approach was implemented to segment the nucleus accumbens, hypothalamus, fornix, mammillary body, basal forebrain and septal nuclei. The cortical, subcortical and white matter components of the Papez circuit were also systematically evaluated. Results: Hexanucleotide repeat expansion carriers exhibited bilateral amygdala, hypothalamus and nucleus accumbens atrophy, and C9orf72 negative patients showed bilateral basal forebrain volume reductions compared to controls. Both patient groups showed left rostral anterior cingulate atrophy, left entorhinal cortex thinning and cingulum and fornix alterations, irrespective of the genotype. Fornix, cingulum, posterior cingulate, nucleus accumbens, amygdala and hypothalamus degeneration was more marked in C9orf72-positive ALS patients. Conclusions: Our results highlighted that mesial temporal and parasagittal subcortical degeneration is not unique to C9orf72 carriers. Our radiological findings were consistent with neuropsychological observations and highlighted the importance of comprehensive neuropsychological testing in ALS, irrespective of the underlying genotype.

20.
Entropy (Basel) ; 26(7)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-39056923

ABSTRACT

A user's devices such as their phone and computer are constantly bombarded by IoT devices and associated applications seeking connection to the user's devices. These IoT devices may or may not seek explicit user consent, thus leaving the users completely unaware the IoT device is collecting, using, and/or sharing their personal data or, only marginal informed, if the user consented to the connecting IoT device but did not read the associated privacy policies. Privacy policies are intended to inform users of what personally identifiable information (PII) data will be collected about them and the policies about how those PII data will be used and shared. This paper presents novel tools and the underlying algorithms employed by the Personal Privacy Assistant app (UTCID PPA) developed by the University of Texas at Austin Center for Identity to inform users of IoT devices seeking to connect to their devices and to notify those users of potential privacy risks posed by the respective IoT device. The assessment of these privacy risks must deal with the uncertainty associated with sharing the user's personal data. If privacy risk (R) equals the consequences (C) of an incident (i.e., personal data exposure) multiplied by the probability (P) of those consequences occurring (C × P), then efforts to control risks must seek to reduce the possible consequences of an incident as well as reduce the uncertainty of the incident and its consequences occurring. This research classifies risk according to two parameters: expected value of the incident's consequences and uncertainty (entropy) of those consequences. This research calculates the entropy of the privacy incident consequences by evaluating: (1) the data sharing policies governing the IoT resource and (2) the type of personal data exposed. The data sharing policies of an IoT resource are scored by the UTCID PrivacyCheck™, which uses machine learning to read and score the IoT resource privacy policies against metrics set forth by best practices and international regulations. The UTCID Identity Ecosystem uses empirical identity theft and fraud cases to assess the entropy of privacy incident consequences involving a specific type of personal data, such as name, address, Social Security number, fingerprint, and user location. By understanding the entropy of a privacy incident posed by a given IoT resource seeking to connect to a user's device, UTCID PPA offers actionable recommendations enhancing the user's control over IoT connections, interactions, their personal data, and, ultimately, user-centric privacy control.

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