BRCA2 promotes genomic integrity and therapy resistance primarily through its role in homology-directed repair.

Tumor suppressor BRCA2 functions in homology-directed repair (HDR), the protection of stalled replication forks, and the suppression of replicative gaps, but their relative contributions to genome integrity and chemotherapy response are under scrutiny. Here, we report that mouse and human cells require a RAD51 filament stabilization motif in BRCA2 for fork protection and gap suppression but not HDR. In mice, the loss of fork protection/gap suppression does not compromise genome stability or shorten tumor latency. By contrast, HDR deficiency increases spontaneous and replication stress-induced chromosome aberrations and tumor predisposition. Unlike with HDR, fork protection/gap suppression defects are also observed in Brca2 heterozygous cells, likely due to reduced RAD51 stabilization at stalled forks/gaps. Gaps arise from PRIMPOL activity, which is associated with 5-hydroxymethyl-2'-deoxyuridine sensitivity due to the formation of SMUG1-generated abasic sites and is exacerbated by poly(ADP-ribose) polymerase (PARP) inhibition. However, HDR proficiency has the major role in mitigating sensitivity to chemotherapeutics, including PARP inhibitors.

DOT1L-mediated RAP80 methylation promotes BRCA1 recruitment to elicit DNA repair.

Breast Cancer Type 1 Susceptibility Protein (BRCA1) is a tumor-suppressor protein that regulates various cellular pathways, including those that are essential for preserving genome stability. One essential mechanism involves a BRCA1-A complex that is recruited to double-strand breaks (DSBs) by RAP80 before initiating DNA damage repair (DDR). How RAP80 itself is recruited to DNA damage sites, however, is unclear. Here, we demonstrate an intrinsic correlation between a methyltransferase DOT1L-mediated RAP80 methylation and BRCA1-A complex chromatin recruitment that occurs during cancer cell radiotherapy resistance. Mechanistically, DOT1L is quickly recruited onto chromatin and methylates RAP80 at multiple lysines in response to DNA damage. Methylated RAP80 is then indispensable for binding to ubiquitinated H2A and subsequently triggering BRCA1-A complex recruitment onto DSBs. Importantly, DOT1L-catalyzed RAP80 methylation and recruitment of BRCA1 have clinical relevance, as inhibition of DOT1L or RAP80 methylation seems to enhance the radiosensitivity of cancer cells both in vivo and in vitro. These data reveal a crucial role for DOT1L in DDR through initiating recruitment of RAP80 and BRCA1 onto chromatin and underscore a therapeutic strategy based on targeting DOT1L to overcome tumor radiotherapy resistance.

GATA3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in breast cancer.

BACKGROUND: Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis. RESULTS: Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor. CONCLUSIONS: These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.

Photodynamic-Assisted Electrochemiluminescence Enhancement toward Advanced BODIPY for Precision Diagnosis of Parkinson.

Nowadays, signal enhancement is imperative to increase sensitivity of advanced ECL devices for expediting their promising applications in clinic. In this work, photodynamic-assisted electrochemiluminescence (PDECL) device was constructed for precision diagnosis of Parkinson, where an advanced emitter was prepared by electrostatically linking 2,6-dimethyl-8-(3-carboxyphenyl)4,4'-difluoroboradiazene (BET) with 1-butyl-3-methylimidazole tetrafluoroborate ([BMIm][BF4]). Specifically, protoporphyrin IX (PPIX) can trigger the photodynamic reaction under light irradiation with a wavelength of 450 nm to generate lots of singlet oxygen (1O2), showing a 2.43-fold magnification in the ECL responses. Then, the aptamer (Apt) was assembled on the functional BET-[BMIm] for constructing a "signal off" ECL biosensor. Later on, the PPIX was embedded into the G-quadruplex (G4) of the Apt to magnify the ECL signals for bioanalysis of α-synuclein (α-syn) under light excitation. In the optimized surroundings, the resulting PDECL sensor has a broad linear range of 100.0 aM ∼ 10.0 fM and a low limit of detection (LOD) of 63 aM, coupled by differentiating Parkinson patients from normal individuals according to the receiver operating characteristic (ROC) curve analysis of actual blood samples. Such research holds great promise for synthesis of other advanced luminophores, combined with achieving an early clinical diagnosis.

Palladium nanospheres-embedded metal-organic frameworks to enhance the ECL efficiency of 2,6-dimethyl-8-(3-carboxyphenyl)4,4'-difluoroboradiazene in aqueous solution for ultrasensitive Cu2+ detection.

Nowadays, organic emitters suffer from insufficient electrochemiluminescence (ECL) efficiency in aqueous solutions, and their practical applications are severely restricted in the bio-sensing field. In this work, palladium nanospheres-embedded metal-organic frameworks (Pd@MOFs) were exploited to enhance the ECL efficiency of 2,6-dimethyl-8-(3-carboxyphenyl)4,4'-difluoroboradiazene (BET) prepared by a one-pot method in aqueous environment. First, the Pd@MOFs were generated via in situ reduction of Pd nanospheres anchored onto the MOFs, and fabricated by orderly coordination of palladium chloride (PdCl2) with 1,2,4,5-benzenetetramine (BTA) tetrahydrochloride. Then, the influence of protons on the ECL response of BET was studied in detail to obtain stronger ECL emission using potassium persulfate (K2S2O8) as co-reactant in aqueous environment. As a result, a 1.47-fold ECL efficiency enlargement of BET/K2S2O8 was harvested at the Pd@MOFs/GCE, where Ru(bpy)32+ behaved as a standard. Based on the fact that the ECL signals of the BET-covered Pd@MOFs modified glassy carbon electrode (simplified as BET/Pd@MOFs/GCE) can be quenched by Cu2+, the as-built ECL sensor showed a wide linear range (1.0-100.0 pM) and a limit of detection (LOD) as low as 0.12 pM. Hence, such research offers huge potential to promote the development of organic emitters in ECL biosensors and environmental monitoring.

Robust point light source calibration method for near-field photometric stereo using feature points selection.

In this paper, we present a robust method for nonisotropic point light source calibration through feature points selection. By analyzing the relationship between the observed surface and its image intensity under near-field lighting, the feature points selection method is first developed to effectively address the noisy observations and improve calibration robustness. Afterward, to enhance efficiency and accuracy of the calibration, a cost function of l p-norm is established based on the above relationship, and an improved Newton method-based iteration process is applied to calculate the light source parameters. The simulations demonstrate that the proposed method is capable of achieving robust calibration results with the estimation error less than 2.7 mm and 0.8°, even though the image intensities are corrupted by Gaussian white noise with standard deviation up to 0.4. The experimental validation is performed using a self-designed photometric stereo system, where the calibration of point light sources is conducted, and measurements are taken on a standard sphere and compressor blade based on the obtained calibration results, which demonstrates the effectiveness of what we believe to be a new method.

Neutrophil Percentage to Albumin Ratio was Associated with Clinical Outcomes in Coronary Care Unit Patients.

Background: Neutrophil percentage to albumin ratio (NPAR) has been shown to be correlated with the prognosis of various diseases. This study aimed to explore the effect of NPAR on the prognosis of patients in coronary care units (CCU). Method: All data in this study were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III, version1.4) database. All patients were divided into four groups according to their NPAR quartiles. The primary outcome was in-hospital mortality. Secondary outcomes were 30-day mortality, 365-day mortality, length of CCU stay, length of hospital stay, acute kidney injury (AKI), and continuous renal replacement therapy (CRRT). A multivariate binary logistic regression analysis was performed to confirm the independent effects of NPAR. Cox regression analysis was performed to analyze the association between NPAR and 365-day mortality. The curve in line with overall trend was drawn by local weighted regression (Lowess). Subgroup analysis was used to determine the effect of NPAR on in-hospital mortality in different subgroups. Receiver operating characteristic (ROC) curves were used to evaluate the ability of NPAR to predict in-hospital mortality. Kaplan-Meier curves were constructed to compare the cumulative survival rates among different groups. Result: A total of 2364 patients in CCU were enrolled in this study. The in-hospital mortality rate increased significantly as the NPAR quartiles increased (p < 0.001). In multivariate logistic regression analysis, NPAR was independently associated with in-hospital mortality (quartile 4 versus quartile 1: odds ratio [OR], 95% confidence interval [CI]: 1.83, 1.20-2.79, p = 0.005, p for trend < 0.001). In Cox regression analysis, NPAR was independently associated with 365-day mortality (quartile 4 versus quartile 1: OR, 95% CI: 1.62, 1.16-2.28, p = 0.005, p for trend < 0.001). The Lowess curves showed a positive relationship between NPAR and in-hospital mortality. The moderate ability of NPAR to predict in-hospital mortality was demonstrated through ROC curves. The area under the curves (AUC) of NPAR was 0.653 (p < 0.001), which is better than that of the platelet to lymphocyte ratio (PLR) (p < 0.001) and neutrophil count (p < 0.001) but lower than the Sequential Organ Failure Assessment (p = 0.046) and Simplified Acute Physiology Score II (p < 0.001). Subgroup analysis did not reveal any obvious interactions in most subgroups. However, Kaplan-Meier curves showed that as NPAR quartiles increased, the 30-day (log-rank, p < 0.001) and 365-day (log-rank, p < 0.001) cumulative survival rates decreased significantly. NPAR was also independently associated with AKI (quartile 4 versus quartile 1: OR, 95% CI: 1.57, 1.19-2.07, p = 0.002, p for trend = 0.001). The CCU and hospital stay length was significantly prolonged in the higher NPAR quartiles. Conclusions: NPAR is an independent risk factor for in-hospital mortality in patients in CCU and has a moderate ability to predict in-hospital mortality.

The Contact Properties of Monolayer and Multilayer MoS2-Metal van der Waals Interfaces.

The contact resistance formed between MoS2 and metal electrodes plays a key role in MoS2-based electronic devices. The Schottky barrier height (SBH) is a crucial parameter for determining the contact resistance. However, the SBH is difficult to modulate because of the strong Fermi-level pinning (FLP) at MoS2-metal interfaces. Here, we investigate the FLP effect and the contact types of monolayer and multilayer MoS2-metal van der Waals (vdW) interfaces using density functional theory (DFT) calculations based on Perdew-Burke-Ernzerhof (PBE) level. It has been demonstrated that, compared with monolayer MoS2-metal close interfaces, the FLP effect can be significantly reduced in monolayer MoS2-metal vdW interfaces. Furthermore, as the layer number of MoS2 increases from 1L to 4L, the FLP effect is first weakened and then increased, which can be attributed to the charge redistribution at the MoS2-metal and MoS2-MoS2 interfaces. In addition, the p-type Schottky contact can be achieved in 1L-4L MoS2-Pt, 3L MoS2-Au, and 2L-3L MoS2-Pd vdW interfaces, which is useful for realizing complementary metal oxide semiconductor (CMOS) logic circuits. These findings indicated that the FLP and contact types can be effectively modulated at MoS2-metal vdW interfaces by selecting the layer number of MoS2.

Imaging characteristics and treatment strategies for carotid artery occlusion caused by skull base fracture: Three case reports.

BACKGROUND: Traumatic internal carotid artery (ICA) occlusion is a rare complication of skull base fractures, characterized by high mortality and disability rates, and poor prognosis. Therefore, timely discovery and correct management are crucial for saving the lives of such patients and improving their prognosis. This article retrospectively analyzed the imaging and clinical data of three patients, to explore the imaging characteristics and treatment strategies for carotid artery occlusion, combined with severe skull base fractures. CASE SUMMARY: This case included three patients, all male, aged 21, 63, and 16 years. They underwent plain film skull computed tomography (CT) examination at the onset of their illnesses, which revealed fractures at the bases of their skulls. Ultimately, these cases were definitively diagnosed through CT angiography (CTA) examinations. The first patient did not receive surgical treatment, only anticoagulation therapy, and recovered smoothly with no residual limb dysfunction (Case 1). The other two patients both developed intracranial hypertension and underwent decompressive craniectomy. One of these patients had high intracranial pressure and significant brain swelling postoperatively, leading the family to choose to take him home (Case 2). The other patient also underwent decompressive craniectomy and recovered well postoperatively with only mild limb motor dysfunction (Case 3). We retrieved literature from PubMed on skull base fractures causing ICA occlusion to determine the imaging characteristics and treatment strategies for this type of disease. CONCLUSION: For patients with cranial trauma combined with skull base fractures, it is essential to complete a CTA examination as soon as possible, to screen for blunt cerebrovascular injury.

Fatigue at the wheel: A non-visual approach to truck driver fatigue detection by multi-feature fusion.

BACKGROUND: Monitoring of long-haul truck driver fatigue state has attracted considerable interest. Conventional fatigue driving detection methods based on the physiological and visual features are scarcely applicable, due to the intrusiveness, reliability, and cost-effectiveness concerns. METHODS: We elaborately developed a fatigue driving detection method by fusion of non-visual features derived from the customized wristbands, vehicle-mounted equipment, and trip logs. To capture the spatiotemporal information within the sequential data, the bidirectional long short-term memory network with attention mechanism was proposed to determine whether the truck driver was fatigued within a fine-grained episode of one minute. The model was validated using a natural driving dataset with nine truck drivers on real-world roads in Guiyang, China during June and July 2021. RESULTS: Our approach yielded 99.21 %, 84.44 %, 82.01 %, 99.63 %, and 83.21 % in accuracy, precision, recall, specificity, and F1-score, respectively. Compared with the mainstream visual-based methods, our approach outperformed particularly in terms of precision and recall. Photoplethysmogram stood out as the most important feature for truck driver fatigue state detection. Vehicle load, driving forward angle, cumulative driving time, midnight, and recent working hours were found to be positively associated with the probability of fatigue driving, while the galvanic skin response, vehicle acceleration, current time, and recent rest hours had a negative relationship. Specifically, truck drivers were more likely to fatigue when driving at 20-40 km/h, braking abruptly at 5-10 m/s2, with vehicle loads over 70 tons, and driving more than 100 min consecutively. CONCLUSIONS: Our study is among the first to harness the natural driving dataset to delve into the real-life fatigue pattern of long-haul truck drivers without disruptions on routine driving tasks. The proposed method holds pragmatic prospects by providing a privacy-preserving, robust, real-time, and non-intrusive technical pathway for truck driver fatigue monitoring.

Development and validation of the Social Touch Experiences and Attitudes Questionnaire-Chinese version (STEAQ-C): How interpersonal touch relates to subclinical traits and symptoms.

Social touch has a vital role in human development and psychological well-being. However, there is a lack of measures assessing individual differences in social touch experiences and attitudes, especially under Eastern cultures. This study developed the Social Touch Experiences and Attitudes Questionnaire - Chinese version (STEAQ-C) and examined its psychometric properties with healthy young Chinese adults. In Study 1, an item pool was generated and principal component analysis (PCA) was used to identify the factor structure of the STEAQ. Study 2 recruited an independent sample and examined its reliability and validity. Network analysis further explored the interrelations between social touch and a variety of subclinical traits and symptoms. PCA identified four factors of the STEAQ-C, relating to childhood touch experiences, current touch with intimate partners, with family and friends, and with unfamiliar people. Study 2 confirmed the four-factor structure and upheld its internal consistency and stability. Positive attitudes towards and greater experiences of social touch were negatively correlated with sensory over-responsiveness and sensory hyposensitivity, as well as childhood trauma particularly emotional neglect, supporting the convergent validity. Evidence of criterion-related validity was accrued via its concurrent and predictive associations with secure attachment style, higher levels of social competence, and lower levels of social anxiety. Network analysis highlighted altered perception of social touch may be a shared feature for psychiatric conditions with social dysfunctions (e.g., autism, social anxiety and negative schizotypy). The newly-developed STEAQ-C may be a timely tool in assessing social touch experiences and attitudes under Eastern cultures.

Suppression of the METTL3-m6A-integrin ß1 axis by extracellular acidification impairs T cell infiltration and antitumor activity.

The acidic metabolic byproducts within the tumor microenvironment (TME) hinder T cell effector functions. However, their effects on T cell infiltration remain largely unexplored. Leveraging the comprehensive The Cancer Genome Atlas dataset, we pinpoint 16 genes that correlate with extracellular acidification and establish a metric known as the "tumor acidity (TuAci) score" for individual patients. We consistently observe a negative association between the TuAci score and T lymphocyte score (T score) across various human cancer types. Mechanistically, extracellular acidification significantly impedes T cell motility by suppressing podosome formation. This phenomenon can be attributed to the reduced expression of methyltransferase-like 3 (METTL3) and the modification of RNA N6-methyladenosine (m6A), resulting in a subsequent decrease in the expression of integrin ß1 (ITGB1). Importantly, enforced ITGB1 expression leads to enhanced T cell infiltration and improved antitumor activity. Our study suggests that modulating METTL3 activity or boosting ITGB1 expression could augment T cell infiltration within the acidic TME, thereby improving the efficacy of cell therapy.

Forecast of peak infection and estimate of excess deaths in COVID-19 transmission and prevalence in Taiyuan City, 2022 to 2023.

In this paper, with the method of epidemic dynamics, we assess the spread and prevalence of COVID-19 after the policy adjustment of prevention and control measure in December 2022 in Taiyuan City in China, and estimate the excess population deaths caused by COVID-19. Based on the transmission mechanism of COVID-19 among individuals, a dynamic model with heterogeneous contacts is established to describe the change of control measures and the population's social behavior in Taiyuan city. The model is verified and simulated by basing on reported case data from November 8th to December 5th, 2022 in Taiyuan city and the statistical data of the questionnaire survey from December 1st to 23rd, 2022 in Neijiang city. Combining with reported numbers of permanent residents and deaths from 2017 to 2021 in Taiyuan city, we apply the dynamic model to estimate theoretical population of 2022 under the assumption that there is no effect of COVID-19. In addition, we carry out sensitivity analysis to determine the propagation character of the Omicron strain and the effect of the control measures. As a result of the study, it is concluded that after adjusting the epidemic policy on December 6th, 2022, three peaks of infection in Taiyuan are estimated to be from December 22nd to 31st, 2022, from May 10th to June 1st, 2023, and from September 5th to October 13th, 2023, and the corresponding daily peaks of new cases can reach 400 000, 44 000 and 22 000, respectively. By the end of 2022, excess deaths can range from 887 to 4887, and excess mortality rate can range from 3.06% to 14.82%. The threshold of the infectivity of the COVID-19 variant is estimated 0.0353, that is if the strain infectivity is above it, the epidemic cannot be control with the previous normalization measures.

PAPAS promotes differentiation of mammary epithelial cells and suppresses breast carcinogenesis.

Extensive remodeling of the female mammary epithelium during development and pregnancy has been linked to cancer susceptibility. The faithful response of mammary epithelial cells (MECs) to hormone signaling is key to avoiding breast cancer development. Here, we show that lactogenic differentiation of murine MECs requires silencing of genes encoding ribosomal RNA (rRNA) by the antisense transcript PAPAS. Accordingly, knockdown of PAPAS derepresses rRNA genes, attenuates the response to lactogenic hormones, and induces malignant transformation. Restoring PAPAS levels in breast cancer cells reduces tumorigenicity and lung invasion and activates many interferon-regulated genes previously linked to metastasis suppression. Mechanistically, PAPAS transcription depends on R-loop formation at the 3' end of rRNA genes, which is repressed by RNase H1 and replication protein A (RPA) overexpression in breast cancer cells. Depletion of PAPAS and upregulation of RNase H1 and RPA in human breast cancer underpin the clinical relevance of our findings.

Tomato bacterial wilt disease outbreaks are accompanied by an increase in soil antibiotic resistance.

The presence of soil-borne disease obstacles and antibiotic resistance genes (ARGs) in soil leads to serious economic losses and health risks to humans. One area in need of attention is the evolution of ARGs as pathogenic soil gradually develops, which introduces uncertainty to the dynamic ability of conventional farming models to predict ARGs. Here, we investigated variations in tomato bacterial wilt disease accompanied by the resistome by metagenomic analysis in soils over 13 seasons of monoculture. The results showed that the abundance and diversity of ARGs and mobile genetic elements (MGEs) exhibited a significant and positive correlation with R. solanacearum. Furthermore, the binning approach indicated that fluoroquinolone (qepA), tetracycline (tetA), multidrug resistance genes (MDR, mdtA, acrB, mexB, mexE), and ß-lactamases (ampC, blaGOB) carried by the pathogen itself were responsible for the increase in overall soil ARGs. The relationships between pathogens and related ARGs that might underlie the breakdown of soil ARGs were further studied in R. solanacearum invasion pot experiments. This study revealed the dynamics of soil ARGs as soil-borne diseases develop, indicating that these ecological trends can be anticipated. Overall, this study enhances our understanding of the factors driving ARGs in disease-causing soils.

Investigation of peri-implant diseases prevalence and related risk indicators in patients with treated severe periodontitis over 4 years after restoration.

Background/purpose: History of periodontitis is a well-documented risk indicator of peri-implantitis. However, the influence of severity of periodontitis is still unclear, especially for severe periodontitis. This study was aimed to investigate the prevalence of peri-implant disease and analyze the risk indicators in patients with treated severe periodontitis. Materials and methods: A total of 182 implants from 88 patients (44 males and 44 females) with severe periodontitis with a mean fellow-up period of 76.5 months were enrolled in this study. Patient and implant information, and periodontal and peri-implant conditions were collected to evaluate the prevalence of peri-implant disease and risk indicators. Results: The prevalence of peri-implantitis was 9.1% and 6.6% at the patient-level and implant-level. The prevalence of peri-implant mucositis was 76.1% and 51.1% at the patient-level and implant-level. Risk indicators of peri-implantitis included older age (OR: 1.132), poor proximal cleaning habits (OR: 14.218), implants in anterior area (OR: 10.36), poor periodontal disease control (OR: 12.76), high peri-implant plaque index (OR: 4.27), and keratinized tissue width (KTW)＜2 mm (OR: 19.203). Conclusion: Implants in patients with severe periodontitis after periodontal treatment and maintenance show a low prevalence (9.1%) of peri-implantitis and a relatively high prevalence (76.2%) of peri-implant mucositis. Patient age, peri-implant proximal cleaning habits, implant position, periodontal disease control, peri-implant plaque index, and KTW are associated with prevalence of peri-implantitis.

Bibliometric and visualized analysis of type 2 diabetic osteoporosis from 2013 to 2022.

Type 2 diabetic osteoporosis (T2DOP) has received increasing attention from researchers. In this study, a total of 453 publications related to T2DOP from 2013 to 2022 were analyzed using bibliometric and visual analysis to identify the research trends and research hotspots in the field of T2DOP. PURPOSE: The objective of this study was to conduct a comprehensive bibliometric analysis of T2DOP-related publications from 2013 to 2022 to determine global research trends in T2DOP in terms of number of publications, countries/regions, institutions, authors, journals, funding agencies, and keywords. METHODS: All data were collected from the Web of Science Core Collection (WoSCC). All original research publications regarding T2DOP from 2013 to 2022 were retrieved. VOSviewer and Microsoft Office Excel were used to conduct the bibliometric and visual analysis. RESULTS: From 2013 to 2022, 515 relevant publications were published, with a peak in 2022 in the annual number of publications. The countries leading the research were USA and China. Sugimoto was the most influential authors. Capital Medical University and Nanjing Medical University were the most prolific institutions. Osteoporosis International was the most productive journal concerning T2DOP research. National Natural Science Foundation of China was the primary funding source for this research area. "Bone-mineral density", "fracture risk", and "postmenopausal women" were the most high-frequency keywords over the past 10 years. CONCLUSION: This was the first bibliometric study of diabetes mellitus and osteoporosis to exclusively examine type 2 diabetes mellitus. Our findings would provide guidance to understand the research frontiers and hot directions in the near future.

Radical Deoxygenative Three-Component Reaction of Alcohols, Aryl Alkenes, and Cyanopyridines.

We report herein a deoxygenative radical multicomponent reaction involving alcohols, aryl alkenes, and cyanopyridine under photoredox conditions. This method is photoredox-neutral, suitable for late-stage modification, and compatible with a wide array of alcohols as alkyl radical sources, including primary, secondary, and tertiary alcohols. This reaction comprises a radical relay mechanism encompassing the Giese addition of aryl alkenes by alkyl radicals, followed by the decyanative pyridination of benzyl radicals.

Predictive models for functional cure in patients with CHB receiving PEG-IFN therapy based on HBsAg quantification through meta-analysis.

BACKGROUND AND AIMS: The efficacy of achieving HBsAg clearance through pegylated interferon (PEG-IFNα) therapy in patients with chronic hepatitis B (CHB) remains uncertain, especially regarding the probability of achieving functional cure among patients with varying baseline HBsAg levels. We aimed to investigate the predictive value of HBsAg quantification for HBsAg seroclearance in CHB patients undergoing PEG-IFNα treatment. METHODS: A systematic search was conducted in PubMed, Embase, and the Cochrane Library up to January 11, 2022. Subgroup analyses were performed for HBeAg-positive and HBeAg-negative patients, PEG-IFNα monotherapy and PEG-IFNα combination therapy, treatment-naive and treatment-experienced patients, and patients with or without liver cirrhosis. RESULTS: This predictive model incorporated 102 studies. The overall HBsAg clearance rates at the end of treatment (EOT) and the end of follow-up (EOF) were 10.6% (95% CI 7.8-13.7%) and 11.1% (95% CI 8.4-14.1%), respectively. Baseline HBsAg quantification was the most significant factor. According to the model, it is projected that when baseline HBsAg levels are 100, 500, 1500, and 10,000 IU/ml, the HBsAg clearance rates at EOF could reach 53.9% (95% CI 40.4-66.8%), 32.1% (95% CI 24.8-38.7%), 14.2% (95% CI 9.8-18.8%), and 7.9% (95% CI 4.2-11.8%), respectively. Additionally, treatment-experienced patients with HBeAg-negative status, and without liver cirrhosis exhibited higher HBsAg clearance rates after PEG-IFNα treatment. CONCLUSION: A successful predictive model has been established to predict the achievement of functional cure in CHB patients receiving PEG-IFNα therapy.

Prediction model for hepatitis B e antigen seroconversion in chronic hepatitis B with peginterferon-alfa treated based on a response-guided therapy strategy.

BACKGROUND: Models for predicting hepatitis B e antigen (HBeAg) seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) after nucleos(t)ide analog treatment are rare. AIM: To establish a simple scoring model based on a response-guided therapy (RGT) strategy for predicting HBeAg seroconversion and hepatitis B surface antigen (HBsAg) clearance. METHODS: In this study, 75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa (PEG-IFNα) treatment and a 24-wk follow-up. Logistic regression analysis was used to assess parameters at baseline, week 12, and week 24 to predict HBeAg seroconversion at 24 wk post-treatment. The two best predictors at each time point were used to establish a prediction model for PEG-IFNα therapy efficacy. Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0. RESULTS: The two most meaningful predictors were HBsAg ≤ 1000 IU/mL and HBeAg ≤ 3 S/CO at baseline, HBsAg ≤ 600 IU/mL and HBeAg ≤ 3 S/CO at week 12, and HBsAg ≤ 300 IU/mL and HBeAg ≤ 2 S/CO at week 24. With a total score of 0 vs 2 at baseline, week 12, and week 24, the response rates were 23.8%, 15.2%, and 11.1% vs 81.8%, 80.0%, and 82.4%, respectively, and the HBsAg clearance rates were 2.4%, 3.0%, and 0.0%, vs 54.5%, 40.0%, and 41.2%, respectively. CONCLUSION: We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNα therapy.