Collaborative Communication: A Qualitative Study of Roles and Emphases of Health Care Providers in Obstetrics and Gynecology.

Purpose: Clinical nursing in obstetrics and gynecology is a technically demanding job. Doctors and nurses have different professional backgrounds and work priorities, and there are differences in communication modes, which can easily lead to poor communication between medical staff and their patients. Therefore this study aims to examine the different communication roles and emphases of obstetrician and gynecologists, nurses and midwives in different sections of SEGUE framework, and further navigate the effectiveness and differences of offline and online provider-patient communication. Participants and Methods: This study employs in-depth interviews to address the research questions. A total of 24 health care providers, including 8 doctors, 5 midwives and 11 nurses, were interviewed face-to-face or by telephone. Results: Doctors pay more attention to the "giving information" stage, while nurses pay more attention to "set the stage" and "elicit information" steps. Midwives and nurses spend more time with patients before and after labor. In addition to information giving, they also accommodate the "understand the patient's perspective" and "end the encounter" steps. Nurses and midwives would attach greater importance to "understanding of patients' perspective". Online medical consultation is more convenient for patients, which can be used as a follow-up complement to offline medical consultation. Conclusion: The health care providers of different types in obstetrics and gynecology communicate collaboratively with patients, highlighting the equally important role of midwives and nurses when communicating with patients. Nurses focus on "set the stage" and "elicit information" stage. Midwife is another important information source and medical care provider, especially for pregnant women in stable conditions. Nutrition clinic of midwife could be recommended for hospitals in second- and third-tier cities, which could help to alleviate obstetricians' workload. The provision of an online collaborative consultation could be beneficial supplement after face-to-face doctor-patient communication.

NIR-II Absorbed Dithienopyrrole-Benzobisthiadiazole Based Nanosystems for Autophagy Inhibition and Calcium Overload Enhanced Photothermal Therapy.

Although the current cancer photothermal therapy (PTT) can produce a powerful therapeutic effect, tumor cells have been proved a protective mechanism through autophagy. In this study, a novel hybrid theranostic nanoparticle (CaCO3@CQ@pDB NPs, CCD NPs) is designed and prepared by integrating a second near-infrared (NIR-II) absorbed conjugated polymer DTP-BBT (pDB), CaCO3, and autophagy inhibitor (chloroquine, CQ) into one nanosystem. The conjugated polymer pDB with asymmetric donor-acceptor structure shows strong NIR-II absorbing capacity, of which the optical properties and photothermal generation mechanism of pDB are systematically analyzed via molecular theoretical calculation. Under NIR-II laser irradiation, pDB-mediated PTT can produce powerful killing ability to tumor cells. At the same time, heat stimulates a large amount of Ca2+ inflow, causing calcium overload induced mitochondrial damage and enhancing the apoptosis of tumor cells. Besides, the released CQ blocks the self-protection mechanism of tumor cells and greatly enhances the attack of PTT and calcium overload therapy. Both in vitro and in vivo experiments confirm that CCD NPs possess excellent NIR-II theranostic capacity, which provides a new nanoplatform for anti-tumor therapy and builds great potential for future clinical research.

Impaired endogenous fibrinolysis status: a potential prognostic predictor in ischemic stroke.

Stroke confers a severe global healthcare burden, hence exploring risk factors for stroke occurrence and prognosis is important for stroke prevention and post-stroke management strategies. Endogenous fibrinolysis is a spontaneous physiological protective mechanism that dissolves thrombus to maintain vascular patency. Recently, impaired endogenous fibrinolysis has been considered as a potential novel cardiovascular risk factor, but its link with ischaemic stroke in the past has been underappreciated. In this review, we summarize the latest mechanisms of endogenous fibrinolysis, review the current evidence and data on endogenous fibrinolysis in ischemic stroke. It includes the structure of thrombus in ischemic stroke patients, the effect of fibrin structure on the endogenous fibrinolytic efficiency, and the association between intravenous thrombolytic therapy and endogenous fibrinolysis in ischemic stroke. It also includes the single factors (tissue plasminogen activator, urokinase plasminogen activator, plasminogen activator inhibitor-1, thrombin activatable fibrinolysis inhibitor, complement component 3, complement component 5, alpha-2-antiplasmin, plasmin-alpha-2-antiplasmin complex, and lipoprotein[a]), and the global assessments of endogenous fibrinolysis status (thromboelastography, rotational thromboelastometry, and global thrombosis test), and their potential as predictors to identify occurrence or unfavorable functional outcomes of ischemic stroke. All of these assessments present advantages and limitations, and we suggest that the global thrombosis test may be more appropriate for detecting impaired endogenous fibrinolysis status in ischemic stroke patients.

A novel controllable capacitor commutation based superconducting hybrid direct current breaker.

Featuring low power loss and high reliability, voltage source converter medium voltage direct current (VSC-MVDC) systems have been widely employed for grid-tied renewable energy applications. To maintain high operational safety, circuit breakers are needed to isolate faulted powerlines by comprehensively considering response speed and installation cost. Research efforts have been put to realizing DC fault isolation by coordinating resistive type superconducting fault current limiter (R-SFCL) and integrated-gate-commutated-thyristor (IGCT) based hybrid DC circuit breaker. In this paper, a controllable current commutation based superconducting DC circuit breaker (CCCB-SDCCB) is proposed. By integrating R-SFCL with IGCT based hybrid DC circuit breakers, the current interrupting capacity can be greatly enlarged with the advantage of low cost and fast speed, and hence the overall cost for suppress large fault currents can be greatly reduced for MVDC systems. In addition, a new current injection circuit branch using H-bridge structure is designed to recycle the residual capacitor voltage from the previous fault stage to trigger the IGCTs without the capacitor pre-charging process. Simulation results show that the fault current can be successfully suppressed from 24.2 to 2.1 kA and fully interrupted within 4.11 ms by the proposed CCCB-SDCCB.

The N6-methyladenosine methylation landscape stratifies breast cancer into two subtypes with distinct immunological characteristics.

N6-methyladenosine (m6A) methylation modification affects the tumorigenesis and metastasis of breast cancer (BC). This study investigated the association between m6A regulator-mediated methylation modification patterns and characterization of the tumour microenvironment in BC, as well as their prognostic importance. Public gene expression data and clinical annotations were collected from The Cancer Genome Atlas (TCGA) database, the Gene Expression Omnibus website and the METABRIC program. We analysed the genetic expression, gene-gene interactions, gene mutations and copy number variations using R software. The data were screened for risk genes using the Cox risk regression model, and we developed an algorithm for risk score and its predictive value. Compared to adjacent normal tissue, we identified 16 differentially expressed m6A regulators in BC, including six writers and 10 readers. Under unsupervised clustering, two distinguished modification patterns were identified, cluster C1 and C2. Compared to m6A cluster C2, cluster C1 was found to be more involved in immune-related pathways, with a relatively higher immune score and stromal score (P < 0.05). Patients were divided into two groups based on their risk scores for survival analysis. The patients in the high-risk score group had significantly worse overall survival than patients in the low-risk score group, (P < 0.0001). The TCGA database validation revealed the same prognostic tendency. In summary, our study showed distinct m6A regulator modification patterns contribute to the immunological heterogeneity and diversity of BC. The development of m6A gene signatures and the m6A score aid in the prognostic prediction of patients with BC.

The effect of rehabilitation time on functional recovery after arthroscopic rotator cuff repair: a systematic review and meta-analysis.

Objective: We compared the effects of early and delayed rehabilitation on the function of patients after rotator cuff repair by meta-analysis to find effective interventions to promote the recovery of shoulder function. Methods: This meta-analysis was registered in PROSPERO (CRD42023466122). We manually searched the randomized controlled trials (RCTs) in the Cochrane Library, Pubmed, Cochrane Library, EMBASE, the China National Knowledge Infrastructure (CNKI), the China VIP Database (VIP), and the Wanfang Database to evaluate the effect of early and delayed rehabilitation after arthroscopic shoulder cuff surgery on the recovery of shoulder joint function. Review Manager 5.3 software was used to analyze the extracted data. Then, the PEDro scale was employed to appraise the methodological quality of the included research. Results: This research comprised nine RCTs and 830 patients with rotator cuff injuries. According to the findings of the meta-analysis, there was no discernible difference between the early rehabilitation group and the delayed rehabilitation group at six and twelve months after the surgery in terms of the VAS score, SST score, follow-up rotator cuff healing rate, and the rotator cuff retear rate at the final follow-up. There was no difference in the ASES score between the early and delayed rehabilitation groups six months after the operation. However, although the ASES score in the early rehabilitation group differed significantly from that in the delayed rehabilitation group twelve months after the operation, according to the analysis of the minimal clinically important difference (MCID), the results have no clinical significance. Conclusions: The improvement in shoulder function following arthroscopic rotator cuff surgery does not differ clinically between early and delayed rehabilitation. When implementing rehabilitation following rotator cuff repair, it is essential to consider the paradoxes surrounding shoulder range of motion and tendon anatomic healing. A program that allows for flexible progression based on the patient's ability to meet predetermined clinical goals or criteria may be a better option.

Monolithic three-dimensional tier-by-tier integration via van der Waals lamination.

Two-dimensional (2D) semiconductors have shown great potential for monolithic three-dimensional (M3D) integration due to their dangling-bonds-free surface and the ability to integrate to various substrates without the conventional constraint of lattice matching1-10. However, with atomically thin body thickness, 2D semiconductors are not compatible with various high-energy processes in microelectronics11-13, where the M3D integration of multiple 2D circuit tiers is challenging. Here we report an alternative low-temperature M3D integration approach by van der Waals (vdW) lamination of entire prefabricated circuit tiers, where the processing temperature is controlled to 120 °C. By further repeating the vdW lamination process tier by tier, an M3D integrated system is achieved with 10 circuit tiers in the vertical direction, overcoming previous thermal budget limitations. Detailed electrical characterization demonstrates the bottom 2D transistor is not impacted after repetitively laminating vdW circuit tiers on top. Furthermore, by vertically connecting devices within different tiers through vdW inter-tier vias, various logic and heterogeneous structures are realized with desired system functions. Our demonstration provides a low-temperature route towards fabricating M3D circuits with increased numbers of tiers.

The effects of acteoside on locomotor recovery after spinal cord injury - The role of autophagy and apoptosis signaling pathway.

In the current study, we investigated the effects of acteoside as a phenylpropanoid glycoside on interaction with neurons to assesses locomotor recovery after spinal cord injury (SCI) in rats by focusing on evaluating the factors involved in autophagy, apoptosis, inflammation and oxidative stress processes. 49 Spargue-Dawley rats were prepared and divided into seven healthy and SCI groups receiving different concentrations of acteoside. After 28 days of disease induction and treatment with acteoside, a BBB score test was used to evaluate locomotor activity. Then, by preparing spinal cord cell homogenates, the expression levels of MAP1LC3A, MAP-2, glial fibrillary acidic protein (GFAP), Nrf2, Keap-1, Caspase 3 (Casp3), Bax, Bcl-2, TNF-a, IL-1B, reactive oxygen species (ROS), and malondialdehyde (MDA) were measured. Improvement of locomotor activity in SCI rats receiving acteoside was observed two weeks after the beginning of the experiment and continued until the fourth week. Both MAP1LC3A and MAP-2 were significantly up-regulated in SCI rats treated with acteoside compared to untreated SCI rats, and GFAP levels were significantly decreased in these animals. Pro-apoptotic proteins Bax and Casp3 and anti-apoptotic protein Bcl-2 were down-regulated and up-regulated, respectively, in SCI rats receiving acteoside. In addition, a significant downregulation of iNOS, TNF-α, and IL-1ß and a decrease in contents of both ROS and MDA as well as increases in Nrf2 and Keap-1 were seen in rats receiving acteoside. Furthermore, acteoside strongly interacted with MAP1LC3A, TNF-α, and Casp3 targets with binding affinities of -8.3 kcal/mol, -8.3 kcal/mol, and -8.5 kcal/mol, respectively, determined by molecular docking studies. In general, it can be concluded that acteoside has protective effects in SCI and can be considered as an adjuvant therapy in the treatment of this disease. However, more studies, especially clinical studies, are needed in this field.

Corrigendum: Bioinformatic analysis of related immune cell infiltration and key genes in the progression of osteonecrosis of the femoral head.

[This corrects the article DOI: 10.3389/fimmu.2023.1340446.].

Traditional, complementary and integrative medicine for fatigue post COVID-19 infection: A systematic review of randomized controlled trials.

Background: Chronic fatigue is a predominant symptom of post COVID-19 condition, or long COVID. We aimed to evaluate the efficacy and safety of Traditional, Complementary and Integrative Medicine (TCIM) for fatigue post COVID-19 infection. Methods: Ten English and Chinese language databases and grey literature were searched up to 12 April 2023 for randomized controlled trials (RCTs). Cochrane "Risk of bias" (RoB) tool was applied. Evidence certainty was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Effect estimates were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Results: Thirteen RCTs with 1632 participants were included. One RCT showed that Bufei Huoxue herbal capsules reduced fatigue (n=129, MD -14.90, 95%CI -24.53 to -5.27), one RCT reported that Ludangshen herbal liquid lowered fatigue (n=184, MD -1.90, 95%CI -2.38 to -1.42), and the other one RCT shown that fatigue disappearance rate was higher with Ludangshen herbal liquid (n=184, RR 4.19, 95%CI 2.06 to 8.53). Compared to traditional Chinese medicine rehabilitation (TCM-rahab) alone, one RCT showed that fatigue symptoms were lower following Qingjin Yiqi granules plus TCM-rehab (n=388, MD -0.48, 95%CI -0.50 to -0.46). Due to concerns with RoB and/or imprecision, the certainty in this evidence was low to very low. No serious adverse events was reported. Conclusions: Limited evidence suggests that various TCIM interventions might reduce post COVID-19 fatigue. Larger, high quality RCTs of longer duration are required to confirm these preliminary findings. Study Registration: The protocol of this review has been registered at PROSPERO: CRD42022384136.

Inhalable spray-dried porous microparticles containing dehydroandrographolide succinate phospholipid complex capable of improving and prolonging pulmonary anti-inflammatory efficacy in mice.

Due to the unique physiological barriers within the lungs, there are considerable challenges in developing drug delivery systems enabling prolonged drug exposure to respiratory epithelial cells. Here, we report a PulmoSphere-based dry powder technology that incorporates a drug-phospholipid complex to promote intracellular retention of dehydroandrographolide succinate (DAS) in respiratory epithelial cells following pulmonary delivery. The DAS-phospholipid complex has the ability to self-assemble into nanoparticles. After spray-drying to produce PulmoSphere microparticles loaded with the drug-phospholipid complex, the rehydrated microparticles discharge the phospholipid complex without altering its physicochemical properties. The microparticles containing the DAS-phospholipid complex exhibit remarkable aerodynamic properties with a fine particle fraction of ∼ 60% and a mass median aerodynamic diameter of ∼ 2.3 µm. These properties facilitate deposition in the alveolar region. In vitro cell culture and lung tissue explants experiments reveal that the drug-phospholipid complex prolongs intracellular residence time and lung tissue retention due to the slow intracellular disassociation of drug from the complex. Once deposited in the lungs, the DAS-phospholipid complex loaded microparticles increase and extend drug exposure to the lung tissues and the immune cells compared to the free DAS counterpart. The improved drug exposure to airway epithelial cells, but not immune cells, is related to a prolonged duration of pulmonary anti-inflammation at decreased doses in a mouse model of acute lung injury induced by lipopolysaccharide. Overall, the phospholipid complex loaded microparticles present a promising approach for improved treatment of respiratory diseases, e.g. pneumonia and acute respiratory distress syndrome.

Podocyte SIRPα reduction aggravates lupus nephritis via promoting T cell inflammatory responses.

Signal-regulatory protein alpha (SIRPα) has recently been found to be highly expressed in podocytes and is essential for maintaining podocyte function. However, its immunoregulatory function in podocytes remains elusive. Here, we report that SIRPα controls podocyte antigen presentation in specific T cell activation via inhibiting spleen tyrosine kinase (Syk) phosphorylation. First, podocyte SIRPα under lupus nephritis (LN) conditions is strongly downregulated. Second, podocyte-specific deletion of SIRPα exacerbates renal disease progression in lupus-prone mice, as evidenced by an increase in T cell infiltration. Third, SIRPα deletion or knockdown enhances podocyte antigen presentation, which activates specific T cells, via enhancing Syk phosphorylation. Supporting this, Syk inhibitor GS-9973 prevents podocyte antigen presentation, resulting in a decrease of T cell activation and mitigation of renal disease caused by SIRPα knockdown or deletion. Our findings reveal an immunoregulatory role of SIRPα loss in promoting podocyte antigen presentation to activate specific T cell immune responses in LN.

Integrating detection and degradation of bisphenol A by photocatalytic fuel cell-driven photoelectrochemical sensor.

To ensure food safety and environmental protection, it is crucial to rapidly identify and remove bisphenol A (BPA), a plasticizer commonly used in the inner lining of food containers and beverage packaging. Here, a photocatalytic fuel cell (PFC)-integrated self-powered photoelectrochemical (PEC) sensor is constructed. Unlike conventional single PEC or PFC sensors, this PFC-integrated PEC sensor relies on not only the difference in Fermi energy levels between photoanode and photocathode but also charge accumulation resulted from the oxidation of BPA by photogenerated holes. Consequently, this sensor achieved a remarkable maximum output power (Pmax) of 8.58 µW cm-2, as well as a high sensitivity, wide linear detection range (0.1-200 µM), low detection limit (0.05 µM), great stability, reproducibility, and real sample detection capability. This work integrates PFC and PEC technologies successfully for the rapid identification and efficient removal of BPA.

POSoligo software for in vitro gene synthesis.

Oligonucleotide synthesis is vital for molecular experiments. Bioinformatics has been employed to create various algorithmic tools for the in vitro synthesis of nucleotides. The main approach to synthesizing long-chain DNA molecules involves linking short-chain oligonucleotides through ligase chain reaction (LCR) and polymerase chain reaction (PCR). Short-chain DNA molecules have low mutation rates, while LCR requires complementary interfaces at both ends of the two nucleic acid molecules or may alter the conformation of the nucleotide chain, leading to termination of amplification. Therefore, molecular melting temperature, length, and specificity must be considered during experimental design. POSoligo is a specialized offline tool for nucleotide fragment synthesis. It optimizes the oligonucleotide length and specificity based on input single-stranded DNA, producing multiple contiguous long strands (COS) and short patch strands (POS) with complementary ends. This process ensures free 5'- and 3'-ends during oligonucleotide synthesis, preventing secondary structure formation and ensuring specific binding between COS and POS without relying on stabilizing the complementary strands based on Tm values. POSoligo was used to synthesize the linear RBD sequence of SARS-CoV-2 using only one DNA strand, several POSs for LCR ligation, and two pairs of primers for PCR amplification in a time- and cost-effective manner.

Spin-Phonon Coupling in Iron-Doped Ultrathin Bismuth Halide Perovskite Derivatives.

Spin in semiconductors facilitates magnetically controlled optoelectronic and spintronic devices. In metal halide perovskites (MHPs), doping magnetic ions is proven to be a simple and efficient approach to introducing a spin magnetic momentum. In this work, we present a facile metal ion doping protocol through the vapor-phase metal halide insertion reaction to the chemical vapor deposition (CVD)-grown ultrathin Cs3BiBr6 perovskites. The Fe-doped bismuth halide (Fe:CBBr) perovskites demonstrate that the iron spins are successfully incorporated into the lattice, as revealed by the spin-phonon coupling below the critical temperature Tc around 50 K observed through temperature-dependent Raman spectroscopy. Furthermore, the phonons exhibit significant softening under an applied magnetic field, possibly originating from magnetostriction and spin exchange interaction. The spin-phonon coupling in Fe:CBBr potentially provides an efficient way to tune the spin and lattice parameters for halide perovskite-based spintronics.

Ovarian Hyperstimulation syndrome combined with hypothyroidism: a comprehensive review.

Ovarian Hyperstimulation Syndrome (OHSS) is a systemic condition marked by the enlargement of the ovaries and heightened vascular permeability. And hypothyroidism (HT) emerges as a potential risk factor for OHSS occurrence. This review presented a comprehensive summary of pertinent case reports involving patients diagnosed with both HT and OHSS. Detailed exploration was conducted into their clinical presentations, diagnostic methodologies, and treatment modalities. Additionally, the review delved into potential interaction mechanisms between HT and OHSS, encompassing various aspects including hormone levels. Moreover, management strategies for mitigating the risk of OHSS in HT patients were thoroughly reviewed and the importance of monitoring thyroid function in those experiencing OHSS was emphasized. This review indicated that the association between HT and OHSS, underscoring its multifaceted complexity. It could accentuate the ongoing necessity for rigorous research and clinical refinement to deepen our comprehension of this association and to bolster diagnostic and therapeutic methodologies for optimal patient care. In conclusion, this review offered valuable insights for future research directions and clinical practices for patients afflicted with OHSS and HT.

Enhancement of ZT in Bi0.5Sb1.5Te3 Thin Film through Lattice Orientation Management.

Thermoelectric power can convert heat and electricity directly and reversibly. Low-dimensional thermoelectric materials, particularly thin films, have been considered a breakthrough for separating electronic and thermal transport relationships. In this study, a series of Bi0.5Sb1.5Te3 thin films with thicknesses of 0.125, 0.25, 0.5, and 1 µm have been fabricated by RF sputtering for the study of thickness effects on thermoelectric properties. We demonstrated that microstructure (texture) changes highly correlate with the growth thickness in the films, and equilibrium annealing significantly improves the thermoelectric performance, resulting in a remarkable enhancement in the thermoelectric performance. Consequently, the 0.5 µm thin films achieve an exceptional power factor of 18.1 µWcm-1K-2 at 400 K. Furthermore, we utilize a novel method that involves exfoliating a nanosized film and cutting with a focused ion beam, enabling precise in-plane thermal conductivity measurements through the 3ω method. We obtain the in-plane thermal conductivity as low as 0.3 Wm-1K-1, leading to a maximum ZT of 1.86, nearing room temperature. Our results provide significant insights into advanced thin-film thermoelectric design and fabrication, boosting high-performance systems.

Robot-assisted total knee arthroplasty system provides more precise control of the femoral rotation angle: A retrospective study.

BACKGROUND: Rotational alignment in total knee arthroplasty (TKA) is a crucial technical point that needs attention. We conducted a retrospective study to investigate whether a new robot-assisted TKA (RA-TKA) could improve the accuracy of rotational alignment and whether rotational alignment affects postoperative pain and functional evaluation of the knee. METHODS: A total of 136 consecutive patients who underwent TKA were included in this study. Half of the patients underwent RA-TKA and the other half underwent conventional TKA (CON-TKA) by the same group of surgeons. Collect the relevant parameters. RESULTS: The postoperative femoral rotation angle (FRA) was -0.72 ± 2.59° in the robot-assisted group and 1.13 ± 2.73° in the conventional group, and were statistically significantly different (p < 0.001). CONCLUSION: This study provides preliminary evidence that the RA-TKA provides more precise control of FRA than CON-TKA, and verifies that tibial rotation angle and combined rotation angle affect postoperative knee pain and functional evaluation.

Precision Colorectal Cancer Fecal Immunological Test Screening With Fecal-Hemoglobin-Concentration-Guided Interscreening Intervals.

Importance: Given a gradient relationship between fecal hemoglobin (f-Hb) concentration and colorectal neoplasia demonstrated previously, using f-Hb-guided interscreening interval has increasingly gained attention in population-based fecal immunological test (FIT), but it is very rare to address how to implement such a precision strategy and whether it can economize the use of FIT and colonoscopy. Objective: To demonstrate the applicability of personalized colorectal cancer (CRC) screening with f-Hb-guided screening intervals to reduce the number of FITs and colonoscopy with as equivalent efficacy as universal biennial screening equivalent efficacy as universal biennial screening. Design, Setting, and Participants: A retrospective cohort study for developing f-Hb-guided precision interscreening interval was conducted using data on a Taiwanese biennial nationwide FIT screening program that enrolled more than 3 million participants aged 50 to 74 years between 2004 and 2014. The cohort was followed up over time until 2019 to ascertain colorectal neoplasia and causes of death. A comparative study was further designed to compare the use of FIT and colonoscopy between the personalized f-Hb-guided group and the universal biennial screening group given the equivalent efficacy of reducing CRC-related outcomes. Main Outcomes and Measurements: A spectrum of f-Hb-guided intervals was determined by using the Poisson regression model given the equivalent efficacy of a universal biennial screening. The use of FIT and colonoscopy for the pragmatic f-Hb-guided interval group was measured compared with the universal biennial screening group. Data analysis was performed from September 2022 to October 2023. Results: Using data from the 3 500 250 participants (mean [SD] age, 57.8 [6.0] years) enrolled in the Taiwanese biennial nationwide FIT screening program, an incremental increase in baseline f-Hb associated with colorectal neoplasia and CRC mortality consistently was observed. Participants with different f-Hb levels were classified into distinct risk categories. Various screening intervals by different f-Hb levels were recommended. Using the proposed f-Hb-guided screening intervals, it was found that the personalized method was imputed to reduce the number of FIT tests and colonoscopies by 49% and 28%, respectively, compared with the universal biennial screening. Conclusion and Relevance: The gradient relationship between f-Hb and colorectal neoplasia and CRC mortality was used to develop personalized FIT screening with f-Hb-guided screening intervals. Such a precision interscreening interval led to the reduced use of FIT test and colonoscopy without compromising the effectiveness of universal biennial screening.

Exploring the Deprotonation Process during Incorporation of a Ligand Water Molecule at the Dangling Mn Site in Photosystem II.

The Mn4CaO5 cluster, featuring four ligand water molecules (W1 to W4), serves as the water-splitting site in photosystem II (PSII). X-ray free electron laser (XFEL) structures exhibit an additional oxygen site (O6) adjacent to the O5 site in the fourth lowest oxidation state, S3, forming Mn4CaO6. Here, we investigate the mechanism of the second water ligand molecule at the dangling Mn (W2) as a potential incorporating species, using a quantum mechanical/molecular mechanical (QM/MM) approach. Previous QM/MM calculations demonstrated that W1 releases two protons through a low-barrier H-bond toward D1-Asp61 and subsequently releases an electron during the S2 to S3 transition, resulting in O•- at W1 and protonated D1-Asp61. During the process of Mn4CaO6 formation, O•-, rather than H2O or OH-, best reproduced the O5···O6 distance. Although the catalytic cluster with O•- at O6 is more stable than that with O•- at W1 in S3, it does not occur spontaneously due to the significantly uphill deprotonation process. Assuming O•- at W2 incorporates into the O6 site, an exergonic conversion from Mn1(III)Mn2(IV)Mn3(IV)Mn4(IV) (equivalent to the open-cubane S2 valence state) to Mn1(IV)Mn2(IV)Mn3(IV)Mn4(III) (equivalent to the closed-cubane S2 valence state) occurs. These findings provide energetic insights into the deprotonation and structural conversion events required for the Mn4CaO6 formation.