Structure-based discovery of novel diarylpyrimidines as potent and selective Non-Nucleoside reverse transcriptase inhibitors: From CH(CN)-Biphenyl-Diarylpyrimidines to CNNH-Biphenyl-Diarylpyrimidines.

In order to enhance the anti-HIV-1 potency and selectivity of the previously reported compound 3 (EC = 27 nM, SI = 1361), a series of novel biphenyl-diarylpyrimidine derivatives were developed by employing structure-based drug design strategy. Among these derivatives, compound M44 demonstrated the most potent inhibitory activity against wild-type (WT) HIV-1 as well as five drug-resistant mutants (EC = 5-148 nM), which were 5-173 times more potent than that of 3 (EC = 27-9810 nM). Furthermore, this analogue exhibited approximately 11-fold lower cytotoxicity (CC = 54 μM) than that of etravirine and rilpivirine.

Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.

Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.

Association between circulating inflammatory proteins and temporomandibular disorders: insight from a two-sample Mendelian randomization analysis.

Background: Past studies have indicated links between specific inflammatory proteins in the bloodstream and temporomandibular disorders (TMDs). Nonetheless, there remains the need for further solid research pinpointing the exact causes behind these associations. This Mendelian randomization (MR) study aims to examine the association between 91 circulating inflammatory proteins and TMDs.

Integrative Quantitative Analysis of Platelet Proteome and Site-Specific Glycoproteome Reveals Diagnostic Potential of Platelet Glycoproteins for Liver Cancer.

The role of peripheral blood platelets as indicators of cancer progression is increasingly recognized, and the significance of abnormal glycosylation in platelet function and related disorders is gaining attention. However, the potential of platelets as a source of protein site-specific glycosylation for cancer diagnosis remains underexplored. In this study, we proposed a general pipeline that integrates quantitative proteomics with site-specific glycoproteomics, allowing for an in-depth investigation of the platelet glycoproteome.

The Effect of PCSK9 Monoclonal Antibodies on Platelet Reactivity and Cardiovascular Events in Patients Receiving Primary Percutaneous Coronary Intervention: A Propensity Score-Matched Analysis.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) have demonstrated promising effects in lowering cardiovascular incidents among patients with acute coronary syndrome. However, their influence on early platelet reactivity after primary percutaneous coronary intervention (PPCI) remains unclear.

Objectives: This research sought to investigate the effects of entirely human anti-PCSK9 antibodies on platelet function as measured by thrombelastography and 12-month postoperative results in patients receiving PPCI and treated with ticagrelor-based dual antiplatelet therapy.

The predictive value of prostate spherical volume ratio in lower urinary tract symptoms and clinical progression of benign prostatic hyperplasia: a retrospective cohort study.

Purpose: To evaluate the predictive value of Prostate Spherical Volume Ratio for Lower urinary tract symptoms and clinical progression of Benign prostatic hyperplasia. And compared with other prostatic anatomical parameters.

Methods: A total of 154 patients with Benign prostatic hyperplasia who underwent MRI and urodynamics were included in the study, while prostate anatomical parameters such as prostate spherical volume ratio, prostate volume, intravesical prostatic protrusion, prostatic urethral length and presumed circle area ratio were determined based on MRI measurements.

Peripheral neuropathy in neuronal intranuclear inclusion disease: a clinical and electrophysiological cross-sectional study.

Background And Objective: Neuronal intranuclear inclusion disease (NIID) is a multifaceted disorder impacting both the central and peripheral nervous systems. This study aims to investigate the clinical and electrophysiological characteristics of peripheral neuropathy in patients with NIID.

Methods: In this cross-sectional study, patients diagnosed with NIID were prospectively recruited from multiple centers across China between October 2017 and May 2024.

In vivo assessment of regional scleral stiffness by shear wave elastography and its association with choroid and retinal nerve fiber layer characteristics in high myopia.

Purpose: To evaluate the posterior scleral stiffness of different regions in high myopic eyes and to explore its associations with macular choroidal and peripapillary retinal nerve fiber layer (pRNFL) thickness and vasculature.

Methods: Thirty subjects with high myopic eyes and 30 subjects with low myopic eyes were included in this study. The elastic modulus of the macular and peripapillary sclera at the temporal, nasal, superior and inferior regions were determined via shear wave elastography (SWE).

A novel hybrid deep learning framework based on biplanar X-ray radiography images for bone density prediction and classification.

Unlabelled: This study utilized deep learning for bone mineral density (BMD) prediction and classification using biplanar X-ray radiography (BPX) images from Huashan Hospital Medical Checkup Center. Results showed high accuracy and strong correlation with quantitative computed tomography (QCT) results. The proposed models offer potential for screening patients at a high risk of osteoporosis and reducing unnecessary radiation and costs.

The role of audiological features and horizontal semicircular canal function at various frequencies in vestibular migraine and Menière's disease.

Background: Vestibular migraine (VM) and Menière's disease (MD) have numerous overlapping symptoms. Distinguishing the two common recurrent vestibulopathies was challenging.

Objectives: To assess the characteristics of hearing loss and the horizontal semicircular canal function in VM and MD.

Inference of Onsager coefficient from microscopic simulations by machine learning.

Dynamic density functional theory (DDFT) is a fruitful approach for modeling polymer dynamics, benefiting from its multiscale and hybrid nature. However, the Onsager coefficient, the only free parameter in DDFT, is primarily derived empirically, limiting the accuracy and broad application of DDFT. Herein, we propose a machine learning-based, bottom-up workflow to directly extract the Onsager coefficient from molecular simulations, circumventing partly heuristic assumptions in traditional approaches.

Constructing Activatable Photosensitizers Using Covalently Modified Mesoporous Silica.

The combination of photosensitizers (PSs) and nanomaterials is a widely used strategy to enhance PS efficacy and broaden their applicability. However, the current nanocarrier-based delivery strategies focus on conventional PSs, neglecting the critical issue of PS phototoxicity. In this study, DHUOCl-25, an activatable PS (aPS) activated by hypochlorous acid, is synthesized by combining a silicon source structure and an activation unit.

Can ACR TI-RADS predict the malignant risk of medullary thyroid cancer?

Objectives: This study aimed to evaluate the diagnostic performance for medullary thyroid cancer (MTC) based on the 2017 Thyroid Imaging Reporting and Data System by the American College of Radiology (ACR TI-RADS) guideline, and the ability to recommend fine needle aspiration (FNA) for MTC.

Methods: Fifty-six MTCs were included, and 168 benign thyroid nodules (BTNs) and 168 papillary thyroid nodules (PTCs) were matched according to age. Ultrasound (US) features were reviewed according to ACR TI-RADS.

Relationships of eating behaviors with psychopathology, brain maturation and genetic risk for obesity in an adolescent cohort study.

Unhealthy eating, a risk factor for eating disorders (EDs) and obesity, often coexists with emotional and behavioral problems; however, the underlying neurobiological mechanisms are poorly understood. Analyzing data from the longitudinal IMAGEN adolescent cohort, we investigated associations between eating behaviors, genetic predispositions for high body mass index (BMI) using polygenic scores (PGSs), and trajectories (ages 14-23 years) of ED-related psychopathology and brain maturation. Clustering analyses at age 23 years ( = 996) identified 3 eating groups: restrictive, emotional/uncontrolled and healthy eaters.

Cumulative blood pressure load and cognitive decline in older adults: An observational analysis of two large cohorts.

Introduction: Cumulative blood pressure metrics may provide greater precision for measuring temporal risk exposure, especially in later life where data are mixed regarding associations of high blood pressure (BP) on cognitive function. We examined the relationship between greater cumulative exposure to high BP in later life and several domains of cognitive function.

Methods: Individual cognitive assessment scores and BP measurements in older adults (age ≥70 years) at baseline and over approximately 8 years of follow-up were available in the population-based Canadian Victoria Longitudinal Study (VLS) and Swedish Gothenburg H70 Birth Cohort Studies (H70).

Prognostic model for esophagogastric variceal rebleeding after endoscopic treatment in liver cirrhosis: A Chinese multicenter study.

Background: Rebleeding after recovery from esophagogastric variceal bleeding (EGVB) is a severe complication that is associated with high rates of both incidence and mortality. Despite its clinical importance, recognized prognostic models that can effectively predict esophagogastric variceal rebleeding in patients with liver cirrhosis are lacking.

Aim: To construct and externally validate a reliable prognostic model for predicting the occurrence of esophagogastric variceal rebleeding.

Evidence summary on management strategies for gastroesophageal reflux symptoms in patients following esophageal cancer surgery.

Objective: This study aimed to summarize evidence-based strategies for the self-management of gastroesophageal reflux symptoms (GERS) at home among patients who have undergone esophageal cancer surgery, providing practical references for clinical practice.

Methods: A systematic evidence summary was conducted based on the reporting standards of the Fudan University Center for Evidence-based Nursing. Literature was retrieved from international and Chinese databases, including guidelines, expert consensus, systematic reviews, and original studies.

Complex management of GS (Good's syndrome) with persistent COVID-19 infection and polymicrobial infections: A case report.

This case report highlights the diagnostic and therapeutic complexities faced by a 56-year-old female with Good's syndrome (GS), who presented with persistent Coronavirus Disease 2019 (COVID-19) infection alongside spp, , and co-infection, which collectively contributed to severe pulmonary involvement. The report further emphasizes a multifaceted treatment approach, incorporating antivirals, antifungals, antimicrobials, immunoglobulins, and antifibrotic therapy, which ultimately led to an improvement in the patient's condition. It underscored the intricate challenges of managing immunocompromised patients with multiple concurrent infections.

Amplification-free detection of using CRISPR-Cas12a and graphene field-effect transistors.

Current molecular tests for tuberculosis (TB), such as whole genome sequencing and Xpert /rifampicin resistance assay, exhibit limited sensitivity and necessitate the pre-amplification step of target DNA. This limitation greatly increases detection time and poses an increased risk of infection. Here, we present a graphene field-effect transistor (GFET) based on the CRISPR/Cas system for detecting .

Quantitative Site-Specific Glycoproteomics Reveals Glyco-Signatures for Breast Cancer Diagnosis.

Intact glycopeptide characterization by mass spectrometry has proven to be a versatile tool for site-specific glycoproteomics analysis and biomarker screening. Here, we present a method using a new model of a Q-TOF instrument equipped with a Zeno trap for intact glycopeptide identification and demonstrate its ability to analyze large-cohort glycoproteomes. From 124 clinical serum samples of breast cancer, noncancerous diseases, and nondisease controls, a total of 6901 unique site-specific glycans on 807 glycosites of proteins were detected.

Protective effects of Notoginsenoside R2 on reducing lipid accumulation and mitochondrial dysfunction in diabetic nephropathy through regulation of c-Src.

Background: The treatment options to delay the progression of diabetic nephropathy (DN), a key contributor to chronic kidney disease (CKD), are urgently needed. Previous studies reported that traditional Chinese medicine Panax notoginseng (PNG) exerted beneficial effects on DN. However, the renoprotective effects of Notoginsenoside R2 (NR2), an active component of PNG, on DN have not been investigated.

Naso-intestinal versus gastric tube for enteral nutrition in patients undergoing mechanical ventilation: a systematic review and meta-analysis.

Background: A systematic appraisal of the comparative efficacy and safety profiles of naso-intestinal tube versus gastric tube feeding in the context of enteral nutrition for mechanically ventilated (MV) patients is imperative. Such an evaluation is essential to inform clinical practice, ensuring that the chosen method of nutritional support is both optimal and safe for this patient population.

Methods: We executed an exhaustive search across PubMed et al.

Impact of central corneal astigmatism on postoperative visual outcomes in patients undergoing trifocal intraocular lens implantation.

Background: To investigate the impact of central corneal astigmatism on postoperative visual outcomes in patients with trifocal intraocular lens (IOL) implantation.

Methods: This retrospective study included 278 eyes of 278 patients who underwent uneventful cataract surgery with implantation of the trifocal IOL (AT LISA tri 839MP). Patients were divided into two groups according to the total corneal refractive power (TCRP) in 3 mm zone centered on the corneal apex: low astigmatism group, TCRP ≤ 0.

Association between COVID-19 anxiety syndrome and COVID-19 vaccine hesitancy in the postpandemic era: a cross-sectional study in Hong Kong.

Background: The COVID-19 pandemic has had profound psychophysiological and socioeconomic effects worldwide. COVID-19 anxiety syndrome (CAS) is a specific cluster of maladaptive coping strategies, including perseveration and avoidance behaviours, in response to the perceived threat and fear of COVID-19. CAS is distinct from general COVID-19 anxiety.

Revealing the decision-making practices in automated external defibrillator deployment: insights from Shanghai, China.

In recent years, the government has promoted the increased deployment of automated external defibrillators (AEDs) in public places with dense crowds, which is of great significance for ensuring that residents enjoy equal health rights. However, it is still unclear what factors decision-makers take into account when formulating deployment plans and whether these factors are related to local characteristics such as population distribution and socioeconomic conditions. Taking Shanghai, China as the research area, we adopted the kernel density estimation and spatial autocorrelation analysis to explore the spatial distribution characteristics of AEDs.