Evaluation of the Stereochemistry of Staphyloferrin A for Developing Staphylococcus-Specific Targeting Conjugates.

Bacteria in the genus Staphylococcus are pathogenic and harmful to humans. Alarmingly, some Staphylococcus, such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) have spread worldwide and become notoriously resistant to antibiotics, threatening and concerning public health. Hence, the development of new Staphylococcus-targeting diagnostic and therapeutic agents is urgent. Here, we chose the S. aureus-secreted siderophore staphyloferrin A (SA) as a guiding unit. We developed a series of Staphyloferrin A conjugates (SA conjugates) and showed the specific targeting ability to Staphylococcus bacteria. Furthermore, among the structural factors we evaluated, the stereo-chemistry of the amino acid backbone of SA conjugates is essential to efficiently target Staphylococci. Finally, we demonstrated that fluorescent Staphyloferrin A probes (SA-FL probes) could specifically target Staphylococci in complex bacterial mixtures.

Two-Step Machine Learning Approach for Charge-Transfer Coupling with Structurally Diverse Data.

Electronic coupling is important in determining charge-transfer rates and dynamics. Coupling strength is sensitive to both intermolecular, e.g., orientation or distance, and intramolecular degrees of freedom. Hence, it is challenging to build an accurate machine learning model to predict electronic coupling of molecular pairs, especially for those derived from the amorphous phase, for which intermolecular configurations are much more diverse than those derived from crystals. In this work, we devise a new prediction algorithm that employs two consecutive KRR models. The first model predicts molecular orbitals (MOs) from structural variation for each fragment, and coupling is further predicted by using the overlap integral included in a second model. With our two-step procedure, we achieved mean absolute errors of 0.27 meV for an ethylene dimer and 1.99 meV for a naphthalene pair, much improved accuracy amounting to 14-fold and 3-fold error reductions, respectively. In addition, MOs from the first model can also be the starting point to obtain other quantum chemical properties from atomistic structures. This approach is also compatible with a MO predictor with sufficient accuracy.

Mitochondria in Retinal Ganglion Cells: Unraveling the Metabolic Nexus and Oxidative Stress.

This review explored the role of mitochondria in retinal ganglion cells (RGCs), which are essential for visual processing. Mitochondrial dysfunction is a key factor in the pathogenesis of various vision-related disorders, including glaucoma, hereditary optic neuropathy, and age-related macular degeneration. This review highlighted the critical role of mitochondria in RGCs, which provide metabolic support, regulate cellular health, and respond to cellular stress while also producing reactive oxygen species (ROS) that can damage cellular components. Maintaining mitochondrial function is essential for meeting RGCs' high metabolic demands and ensuring redox homeostasis, which is crucial for their proper function and visual health. Oxidative stress, exacerbated by factors like elevated intraocular pressure and environmental factors, contributes to diseases such as glaucoma and age-related vision loss by triggering cellular damage pathways. Strategies targeting mitochondrial function or bolstering antioxidant defenses include mitochondrial-based therapies, gene therapies, and mitochondrial transplantation. These advances can offer potential strategies for addressing mitochondrial dysfunction in the retina, with implications that extend beyond ocular diseases.

Oncological outcomes of large gastrointestinal stromal tumors treated by laparoscopic resection.

BACKGROUND: The resection of large gastric gastrointestinal stromal tumors (GISTs) by laparoscopic has been controversial. Extending from our prior study, the long-term oncological outcome of laparoscopic resection of large (5-8 cm) gastric GISTs was reported. METHODS: From 2002 to 2018, a consecutive 66 patients with gastric GISTs of 5-8 cm were treated at National Taiwan University Hospital. Among them, 30 patients received open surgery, and 36 received laparoscopic surgery. The clinicopathological data, peri-operative and oncological outcomes were compared between groups. RESULTS: The clinical demographics including sex, age, BMI, tumor locations and ratio of wedge resection were similar between groups. The mean tumor size was 6.0 ± 0.83 cm versus 6.3 ± 1.07 cm (Open vs. Laparoscopic, p = 0.3). The operation time, blood loss, and post-operative complications, were also similar. The mean hospital stay was shorter in the laparoscopic group (8.8 ± 2.5 days) than in the open group (12.0 ± 8.9 days), though not significantly different. The median follow-up time was 108 ± 58 months (97 ± 50 in laparoscopic group; 122 ± 64 in open group). All except three patients remain disease-free. One in the open group and two in the laparoscopic group had recurrence of tumor, and they were stable of disease under Imatinib treatment. Eight patients died in non-GIST causes during follow-up. The 5-year recurrence-free survival were 100% for the open and 94.2% for the laparoscopic group (p = 0.2). CONCLUSION: Our data showed that laparoscopic surgery for gastric GIST between 5 and 8 cm was safe and oncologically feasible.

Effectiveness of mental health website intervention on stress and depression for women with recurrent miscarriage: A randomized controlled trial.

We aimed to investigate the effect of a mental health website intervention on perceived stress, depression, sleep quality, and social support in women with recurrent miscarriage (RM). Performing a randomized controlled trial, the participants in the experimental group (n = 31) received a 12-week mental health website intervention; the participants in the control group (n = 31) received RM standard medical care only. The paired t-tests results for the mean posttest scores for depression (p = .023) and perceived stress (p = .041) in the experimental group showed a significant decrease, but did not in the control group.

Infrapatellar fat pad-derived mesenchymal stromal cell product for treatment of knee osteoarthritis: a first-in-human study with evaluation of the potency marker.

BACKGROUND AIMS: Infrapatellar fat pad-derived mesenchymal stromal cells (IFP-MSCs) have not yet been used in a human clinical trial. In this open-label phase 1 study, patients with knee osteoarthritis (OA) received a single intra-articular injection of autologous IFP-MSCs. Safety was assessed through physical examination of the knee joint, vital signs, laboratory tests and adverse events. Efficacy was evaluated with regard to pain and function using questionnaires, x-ray and magnetic resonance imaging (MRI). Indoleamine-2,3-dioxygenase (IDO) expression in IFP-MSCs primed with interferon gamma was used as an in vitro potency measurement in investigating the correlations of clinical outcomes. METHODS: Twelve patients with symptomatic knee OA were recruited. IFP adipose tissue was harvested from each patient's knee through surgical excision for IFP-MSC manufacturing. Cryopreserved IFP-MSCs (5 × 107 cells) were injected into the knee joint immediately after thawing. RESULTS: No significant adverse events were observed. Patients who received IFP-MSCs exhibited clinically significant pain and functional improvement at 48-week follow-up. The MRI Osteoarthritis Knee Score average was also significantly reduced from 100.2 before injection to 85.0 at 48 weeks after injection. The IDO expression of the primed IFP-MSCs of the 12 patients was correlated with clinical outcomes after injection. CONCLUSIONS: A single intra-articular injection of IFP-MSCs appears to be a safe therapy for treating knee OA and may improve disease symptoms. IDO measurement of primed IFP-MSCs has potential as a potency marker of MSC products for immunomodulatory therapy.

Analytical gradients and derivative couplings for the TDDFT-1D method.

We derive and implement analytic gradients and derivative couplings for time-dependent density functional theory plus one double (TDDFT-1D) which is a semiempirical configuration interaction method whereby the Hamiltonian is diagonalized in a basis of all singly excited configurations and one doubly excited configuration as constructed from a set of reference Kohn-Sham orbitals. We validate the implementation by comparing against finite difference values. Furthermore, we show that our implementation can locate both optimized geometries and minimum-energy crossing points along conical seams of S1/S0 surfaces for a set of test cases.

Electron transfer and spin-orbit coupling: Can nuclear motion lead to spin selective rates?

We investigate a spin-boson inspired model of electron transfer, where the diabatic coupling is given by a position-dependent phase, eiWx. We consider both equilibrium and nonequilibrium initial conditions. We show that, for this model, all equilibrium results are completely invariant to the sign of W (to infinite order). However, the nonequilibrium results do depend on the sign of W, suggesting that photo-induced electron transfer dynamics with spin-orbit coupling can exhibit electronic spin polarization (at least for some time).

Laparoscopic versus open distal gastrectomy for elderly patients with advanced gastric cancer: a retrospective comparative study.

BACKGROUND: Laparoscopic radical distal gastrectomy (LDG) has been more frequently performed for locally advanced distal gastric cancer (AGC) than open distal gastrectomy (ODG). However, the benefits of LDG for elderly AGC patients (AGC-lap) remain unclear. METHODS: Patients aged ≥ 70 years who underwent D2 distal gastrectomy from July 2014 to July 2021 were enrolled consecutively. Perioperative parameters, pathological features, and oncological outcomes of AGC-lap patients (n = 39) were compared with those of elderly AGC patients receiving ODG (AGC-open; n = 37) and elderly early gastric cancer patients receiving LDG (EGC-lap; n = 41) respectively. RESULTS: The median age of all AGC patients was 77 years, and 28% of them had an Eastern Cooperative Oncology Group score ≥ 2. Most of the perioperative and pathological features (including the number of lymph nodes harvested) were similar between the AGC-lap and AGC-open groups. AGC-lap patients had longer median operative times (215 min versus 192 min) but significantly less surgical complications (10.3% versus 37.8%) and shorter median hospital stays (11 days versus 13 days) than did AGC-open patients (all p < 0.05). The 3-year recurrence-free and overall survival was 66.2% and 88.8% in the AGC-lap group and 51% and 66.3% in the AGC-open group (both p = 0.1). The perioperative features, including operative time, number of lymph nodes harvested, hospital stay, and complication rates, were similar between the AGC- and EGC-lap groups. CONCLUSIONS: LDG was safely and effectively performed in elderly AGC patients, resulting in faster recovery and a lower complication rate than ODG, without compromising oncological outcomes.

HSPA4 Is a Biomarker of Placenta Accreta and Enhances the Angiogenesis Ability of Vessel Endothelial Cells.

Placenta accreta spectrum (PAS) accounts for 7% of maternal mortality and is associated with intraoperative and postoperative morbidity caused by massive blood loss, infection, and adjacent organ damage. The aims of this study were to identify the protein biomarkers of PAS and to further explore their pathogenetic roles in PAS. For this purpose, we collected five placentas from pregnant subjects with PAS complications and another five placentas from normal pregnancy (NP) cases. Then, we enriched protein samples by specifically isolating the trophoblast villous, deeply invading into the uterine muscle layer in the PAS patients. Next, fluorescence-based two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-TOF/MS were used to identify the proteins differentially abundant between PAS and NP placenta tissues. As a result, nineteen spots were determined as differentially abundant proteins, ten and nine of which were more abundant in PAS and NP placenta tissues, respectively. Then, specific validation with western blot assay and immunohisto/cytochemistry (IHC) assay confirmed that heat shock 70 kDa protein 4 (HSPA4) and chorionic somatomammotropin hormone (CSH) were PAS protein biomarkers. Further tube formation assays demonstrated that HSPA4 promoted the in vitro angiogenesis ability of vessel endothelial cells, which is consistent with the in vivo scenario of PAS complications. In this study, we not only identified PAS protein biomarkers but also connected the promoted angiogenesis with placenta invasion, investigating the pathogenetic mechanism of PAS.

Congenital Stationary Night Blindness: Clinical and Genetic Features.

Congenital stationary night blindness (CSNB) is an inherited retinal disease (IRD) that causes night blindness in childhood with heterogeneous genetic, electrophysical, and clinical characteristics. The development of sequencing technologies and gene therapy have increased the ease and urgency of diagnosing IRDs. This study describes seven Taiwanese patients from six unrelated families examined at a tertiary referral center, diagnosed with CSNB, and confirmed by genetic testing. Complete ophthalmic exams included best corrected visual acuity, retinal imaging, and an electroretinogram. The effects of identified novel variants were predicted using clinical details, protein prediction tools, and conservation scores. One patient had an autosomal dominant CSNB with a RHO variant; five patients had complete CSNB with variants in GRM6, TRPM1, and NYX; and one patient had incomplete CSNB with variants in CACNA1F. The patients had Riggs and Schubert-Bornschein types of CSNB with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. This is the first report of CSNB patients in Taiwan with confirmed genetic testing, providing novel perspectives on molecular etiology and genotype-phenotype correlation of CSNB. Particularly, variants in TRPM1, NYX, and CACNA1F in our patient cohort have not previously been described, although their clinical significance needs further study. Additional study is needed for the genotype-phenotype correlation of different mutations causing CSNB. In addition to genetic etiology, the future of gene therapy for CSNB patients is reviewed and discussed.

[Community Innovation and Regional Sustainability: The Practice of Time Banking at Fooyin University].

The need for health literacy in the context of older adult healthcare has increased significantly with population aging. Employing innovative models of social service delivery will be necessary to effectively integrate academic, medical, and community resources to address diverse healthcare needs. The project of university social responsibility supported by Fooyin University is a comprehensive program that employs a time bank model and cultivates community. The Fooyin Time Bank leverages reciprocity to cultivate sustainable manpower to satisfy community needs. The five strategies of the Fooyin Time Bank include: 1) strengthen the awareness of the time bank in community volunteers, 2) cultivate seed members to initiate the time bank, 3) adapt the mutual help model to meet local individual needs, 4) promote the online platform system of the time banking infrastructure and diversities of resource exchange, and 5) emphasize the key role of community and supplementary role of university to enhance sustainability. The Fooyin Time Bank coordinates with government agencies, private companies, and academic institutions to bolster the sustainability of its networks. In addition, faculties and students participate in the community to create a social climate of mutual help, inter-generational aged care, and social welfare.

Associated Learning: Decomposing End-to-End Backpropagation Based on Autoencoders and Target Propagation.

Backpropagation (BP) is the cornerstone of today's deep learning algorithms, but it is inefficient partially because of backward locking, which means updating the weights of one layer locks the weight updates in the other layers. Consequently, it is challenging to apply parallel computing or a pipeline structure to update the weights in different layers simultaneously. In this letter, we introduce a novel learning structure, associated learning (AL), that modularizes the network into smaller components, each of which has a local objective. Because the objectives are mutually independent, AL can learn the parameters in different layers independently and simultaneously, so it is feasible to apply a pipeline structure to improve the training throughput. Specifically, this pipeline structure improves the complexity of the training time from O(nℓ), which is the time complexity when using BP and stochastic gradient descent (SGD) for training, to O(n+ℓ), where n is the number of training instances and ℓ is the number of hidden layers. Surprisingly, even though most of the parameters in AL do not directly interact with the target variable, training deep models by this method yields accuracies comparable to those from models trained using typical BP methods, in which all parameters are used to predict the target variable. Consequently, because of the scalability and the predictive power demonstrated in the experiments, AL deserves further study to determine the better hyperparameter settings, such as activation function selection, learning rate scheduling, and weight initialization, to accumulate experience, as we have done over the years with the typical BP method. In addition, perhaps our design can also inspire new network designs for deep learning. Our implementation is available at https://github.com/SamYWK/Associated_Learning.

On the inclusion of one double within CIS and TDDFT.

We present an improved approach for generating a set of optimized frontier orbitals (HOMO and LUMO) that minimizes the energy of one double configuration. We further benchmark the effect of including such a double within a rigorous configuration interaction singles or a parameterized semi-empirical time-dependent density functional theory Hamiltonian for a set of test cases. Although we cannot quite achieve quantitative accuracy, the algorithm is quite robust and routinely delivers an enormous qualitative improvement to standard single-reference electronic structure calculations.

Modeling nonadiabatic dynamics with degenerate electronic states, intersystem crossing, and spin separation: A key goal for chemical physics.

We examine the many open questions that arise for nonadiabatic dynamics in the presence of degenerate electronic states, e.g., for singlet-to-triplet intersystem crossing where a minimal Hamiltonian must include four states (two of which are always degenerate). In such circumstances, the standard surface hopping approach is not sufficient as the algorithm does not include Berry force. Yet, we hypothesize that such a Berry force may be crucial as far as creating chiral induced spin separation, which is now a burgeoning field of study. Thus, this Perspective highlights the fact that if one can generate a robust and accurate semiclassical approach for the case of degenerate states, one will take a big step forward toward merging chemical physics with spintronics.

Adjuvant tegafur-uracil (UFT) or S-1 monotherapy for advanced gastric cancer: a single center experience.

BACKGROUND: Adjuvant tegafur-gimeracil-oteracil (S-1) is commonly used for gastric cancer in Asia, and tegafur-uracil (UFT) is another oral fluoropyrimidine when S-1 is unavailable. The real-world data of adjuvant UFT has less been investigated. METHODS: Patients with pathological stage II-IIIB (except T1) gastric cancer receiving adjuvant UFT or S-1 monotherapy after D2 gastrectomy were included. Usage of UFT or S-1 was based on reimbursement policy of the Taiwanese healthcare system. The characteristics, chemotherapy completion rates, and 5-year recurrence-free survival (RFS) and overall survival (OS), were compared between these two groups. RESULTS: From 2005 to 2016, 86 eligible patients were included. Most tumor characteristics were similar between the UFT group (n = 37; age 59.1 ± 13.9 years) and S-1 group (n = 49; age 56.3 ± 10.7 years), except there were significantly more Borrmann type III/IV (86.5% versus 67.3%; p = 0.047) and T4 (56.8% versus 10.2%; p < 0.001) lesions in the UFT group than in the S-1 group. The chemotherapy complete rates were similar in the two groups. The 5-year RFS was 56.1% in the UFT group and 59.6% in the S-1 group (p = 0.71), and the 5-year OS was 78.3% in the UFT group and 73.1% in the S-1 group (p = 0.48). The hazard ratio of adjuvant chemotherapy (S-1 versus UFT) on RFS was 1.25 (95% confidence interval = 0.53-2.94) when Borrmann type and T and N stages were adjusted. CONCLUSIONS: This small cohort study showed adjuvant UFT, and S-1 monotherapy had a comparable long-term outcome for pathological stage II-IIIB gastric cancer following D2 gastrectomy.

Outcomes of a walking exercise intervention in postpartum women with disordered sleep.

AIM: Good sleep quality is essential to physical and mental-health-related quality of life. The purpose of this study was to evaluate the effects of a walking exercise in relieving sleep quality, fatigue, and depression in new mothers during the postpartum period. METHODS: This quasi-experimental study was conducted at a teaching hospital in southern Taiwan. One hundred and four eligible postpartum women with poor sleep quality (Postpartum Sleep Quality Scale; PSQS score ≧16) were assigned to either the experimental group (n = 50) or the control group (n = 54) according to their individual preferences. The participants in the experimental group participated in a 12-week stride walking exercise intervention. The control group did not receive any exercise intervention. The PSQS, Postpartum Fatigue Scale, and Edinburgh Postnatal Depression Scale were used to assess outcomes. RESULTS: Repeated measures ANOVA demonstrated that the experimental group participants perceived milder physical symptoms associated with sleep inefficiency at 4-week posttest (F = 7.25, p < 0.01) than their control group peers. However, no significant differences were found between two groups in terms of either fatigue or depression at 4-week and 12-week posttest. CONCLUSION: Significant improvement in the physical symptoms associated with sleep inefficiency was observed. The findings may be used to encourage postpartum women with disordered sleep to incorporate 20-30 min of stride walking into their regular routine to improve sleep quality.

Assessing the quality of electronic medical records as a platform for resident education.

BACKGROUND: Previous studies have assessed note quality and the use of electronic medical record (EMR) as a part of medical training. However, a generalized and user-friendly note quality assessment tool is required for quick clinical assessment. We held a medical record writing competition and developed a checklist for assessing the note quality of participants' medical records. Using the checklist, this study aims to explore note quality between residents of different specialties and offer pedagogical implications. METHODS: The authors created an inpatient checklist that examined fundamental EMR requirements through six note types and twenty items. A total of 149 records created by residents from 32 departments/stations were randomly selected. Seven senior physicians rated the EMRs using a checklist. Medical records were grouped as general medicine, surgery, paediatric, obstetrics and gynaecology, and other departments. The overall and group performances were analysed using analysis of variance (ANOVA). RESULTS: Overall performance was rated as fair to good. Regarding the six note types, discharge notes (0.81) gained the highest scores, followed by admission notes (0.79), problem list (0.73), overall performance (0.73), progress notes (0.71), and weekly summaries (0.66). Among the five groups, other departments (80.20) had the highest total score, followed by obstetrics and gynaecology (78.02), paediatrics (77.47), general medicine (75.58), and surgery (73.92). CONCLUSIONS: This study suggested that duplication in medical notes and the documentation abilities of residents affect the quality of medical records in different departments. Further research is required to apply the insights obtained in this study to improve the quality of notes and, thereby, the effectiveness of resident training.

High-Mobility Semiconducting Two-Dimensional Conjugated Covalent Organic Frameworks with p-Type Doping.

Two-dimensional conjugated covalent organic frameworks (2D c-COFs) are emerging as a unique class of semiconducting 2D conjugated polymers for (opto)electronics and energy storage. Doping is one of the common, reliable strategies to control the charge carrier transport properties, but the precise mechanism underlying COF doping has remained largely unexplored. Here we demonstrate molecular iodine doping of a metal-phthalocyanine-based pyrazine-linked 2D c-COF. The resultant 2D c-COF ZnPc-pz-I2 maintains its structural integrity and displays enhanced conductivity by 3 orders of magnitude, which is the result of elevated carrier concentrations. Remarkably, Hall effect measurements reveal enhanced carrier mobility reaching ∼22 cm2 V-1 s-1 for ZnPc-pz-I2, which represents a record value for 2D c-COFs in both the direct-current and alternating-current limits. This unique transport phenomenon with largely increased mobility upon doping can be traced to increased scattering time for free charge carriers, indicating that scattering mechanisms limiting the mobility are mitigated by doping. Our work provides a guideline on how to assess doping effects in COFs and highlights the potential of 2D c-COFs to display high conductivities and mobilities toward novel (opto)electronic devices.

Analytic gradients and derivative couplings for configuration interaction with all single excitations and one double excitation-En route to nonadiabatic dynamics.

We present analytic gradients and derivative couplings for the simplest possible multireference configuration interaction method, CIS-1D, an electronic structure Ansatz that includes all single excitations and one lone double excitation on top of a Hartree-Fock reference state. We show that the resulting equations are numerically stable and require the evaluation of a similar number of integrals as compared to standard CIS theory; one can easily differentiate the required frontier orbitals (h and l) with minimal cost. The resulting algorithm has been implemented within the Q-Chem electronic structure package and should be immediately useful for understanding photochemistry with S0-S1 crossings.