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Objective: To evaluate the efficacy of CO2 fractional laser and microneedling pretreatment combined with ALA-PDT for moderate-to-severe acne, aiming to optimize clinical treatment., Methods: Patients were randomly divided into three groups: Group A (CO2 fractional laser + ALA-PDT), Group B (microneedling + ALA-PDT), and Group C (ALA-PDT). Each group underwent photodynamic therapy once a week for 3 weeks. Efficacy was assessed at the end of the 4th week, and recurrence was assessed at the end of the 12th week., Results: A total of 150 patients with moderate to severe acne were included in this study, with 50 patients in each group. Four weeks after the end of treatment, the effective rates were 88 % for Group A, 62 % for Group B, and 36 % for Group C. Statistically significant differences were found between the groups (P < 0.05), with Group A showing superior efficacy compared to Group B (P < 0.05). No serious systemic or local adverse reactions were observed in any group. No recurrence was seen in any group 12 weeks after the end of treatment, and some patients continued to show improvement in skin lesions over time., Conclusion: Both the CO2 fractional laser group and the microneedling group improved the efficacy of photodynamic therapy for moderate to severe acne compared to the control group, with the CO2 fractional laser group demonstrating better efficacy and fewer adverse effects., (Copyright © 2024. Published by Elsevier B.V.)

Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of unknown etiology that commonly affects adolescents, imposing significant socioeconomic burdens. Effective management necessitates a comprehensive approach that takes into account multiple factors, including growth potential and psychological issues. Despite significant advancements in AIS management, several questions regarding optimal treatment strategies persist. Recent technological advancements are transforming the treatment landscape, encompassing advancements in bracing, robotic-assisted deformity corrections, and other interventions. This review explores current issues debated in the literature concerning the treatment of AIS, focusing on contemporary high-level evidence (e.g., meta-analyses and randomized controlled trials). Furthermore, this review explores cutting-edge developments and future directions in AIS management, including the integration of artificial intelligence and augmented reality.

In this paper, we investigate the phase behavior of a surfactant mixture comprising glyceryl stearate, potassium stearate, and stearic acid, in the presence of Carbopol, a commonly used thickener in personal care products. At low Carbopol concentrations (<0.03%), the surfactant mixture interacted with Carbopol electrostatically, increasing the degree of Carbopol swelling and, consequently, the overall viscosity. However, such an effect diminished as the Carbopol concentration was further increased. At a Carbopol concentration of 0.2%, two types of liquid crystalline surfactant structures, namely, multilamellar vesicles and lamellae, were observed between the swollen Carbopol domains. Although similar types of surfactant structures were present in a much more concentrated surfactant solution having a similar viscosity but without Carbopol, the lamellae in the presence of Carbopol were more ordered and with a larger d spacing. The increased ordering was probably induced by the interactions between the surfactants and Carbopol as the surfactants were confined between the swollen Carbopol domains.

The unique architecture of the brain and the blood-brain barrier imposes challenges for the measurement of parenchyma-derived biomarkers that prevent sufficient understanding of transient neuropathogenic processes. One solution to this challenge is direct sampling of brain interstitial fluid via implanted microperfusion probes. Seeking to understand spatial limitations to microperfusion in the brain, we employed computational fluid dynamics modeling and empirical recovery of fluorescently labeled dextrans in an animal model. We found that dextrans were successfully recovered via microperfusion over a 6 h sampling period, especially at probes implanted 2 mm from the dextran infusion point relative to probes implanted 5 mm from the injection site. Experimental recovery was consistently around 1% of simulated, suggesting that this parameter can be used to set practical limits on the maximal tissue concentration of proteins measured in microperfusates and on the spatial domain sampled by our multimodal microperfusion probe.

This study investigates the impact of the anatomical separation point of the dorsal ulnar cutaneous nerve (DUCN) on nerve conduction studies (NCS). Involving 25 subjects with DUCN NCS findings, it utilizes ultrasound to mark the DUCN's divergence from the ulnar nerve. NCS was performed at four points relative to the separation point. The findings indicate the maximal amplitudes occurred 2 cm distal to the separation point. The study suggests it is ideal when the stimulation is performed between the seperation point and 2 cm distal to it., (© 2024. The Author(s).)

Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, is metabolized through hepatic cytochrome P450 (CYP), specifically CYP3A1/2 and CYP2C11. Prolonged administration of rheumatoid arthritis medications is generally associated with an increased risk of renal toxicity. Loganin (LGN), an iridoid glycoside, has hepatorenal regenerative properties. This study investigates the potential of LGN to mitigate acute kidney injury (AKI) and its effects on the pharmacokinetics of tofacitinib in rats with cisplatin-induced AKI. Both intravenous and oral administration of tofacitinib to AKI rats significantly increased the area under the plasma concentration-time curve from time 0 to infinity (AUC) compared with control (CON) rats, an increase attributed to the decelerated non-renal clearance (CL NR ) and renal clearance (CL R ) of tofacitinib. Administration of LGN to AKI rats, however, protected kidneys from severe impairment, restoring the pharmacokinetic parameters (AUC, CL NR , and CL R ) of tofacitinib to those observed in untreated CON rats, with partial recovery of kidney function, as evidenced by an increase in creatinine clearance (CL CR ). Possible interactions between drugs and natural components should be considered, especially when co-administering both a drug and a natural extract containing LGN or iridoid glycosides to patients with kidney injury.

This study aims to explore the inhibitory effect of daidzein on macrophage inflammation induced by high glucose via regulating the NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. The cell counting kit-8(CCK-8) assay was employed to detect the effects of daidzein at different concentrations on the viability of RAW264.7 cells. Western blot was employed to determine the protein level of tumor necrosis factor(TNF)-α in macrophages exposed to different concentrations of glucose for different time periods as well as the expression levels of proteins involved in the polarization and Toll-like receptor 4(TLR4)-myeloid differentiation factor(MyD88)-NLRP3 inflammasome pathway of the macrophages exposed to high glucose. Enzyme-linked immunosorbent assay was employed to measure the levels of TNF-α, interleukin(IL)-18, and IL-1β secreted by macrophages. The expression level of nuclear factor-kappa B(NF-κB) p65 in macrophages exposed to high glucose was detected by immunofluorescence, and the level of intracellular reactive oxygen species(ROS) was detected by the DCFH-DA fluorescent probe. The mRNA levels of NLRP3, TNF-α, and IL-18 in macrophages were determined by qRT-PCR. The results showed that treatment with 30 mmol·L~(-1) glucose for 48 h was the best condition for the modeling of macrophage injury. Compared with the blank group, the model group showed improved polarization of macrophages, increased secretion of TNF-α, IL-18, and IL-1β, elevated ROS level, and up-regulated expression of NF-κB p65. In addition, the modeling up-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 and the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1β, cleaved IL-1β, and pro-IL-18. Compared with the model group, daidzein(10, 20, and 40 μmol·L~(-1)) lowered the levels of inflammatory cytokines and down-regulated the mRNA levels of NLRP3, TNF-α, and IL-18 as well as the protein levels of TLR4, MyD88, NLRP3, NF-κB p65, p-NF-κB p65, I-κB, p-I-κB, ASC, pro-caspase-1, pro-IL-1β, cleaved IL-1β, and pro-IL-18. In addition, daidzein reduced intracellular ROS. According to the available reports and the experimental results, high glucose can induce the polarization of macrophages and promote the secretion of inflammatory cytokines. Daidzein can inhibit the expression of ROS in macrophages by regulating the NLRP3 inflammasome signaling pathway, thereby reducing the inflammation of macrophages exposed to high glucose.

Objective: We present low-level mosaic trisomy 14 at amniocentesis., Case Report: A 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer (IVF-ET). Amniocentesis revealed a karyotype of 47,XX,+14 [4]/46,XX [27], consistent with 12.9% mosaicism for trisomy 14. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1-22, X) × 2 with no genomic imbalance. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling at 21 weeks of gestation and was offered expanded non-invasive prenatal testing (NIPT) which was positive for trisomy 14. At 24 weeks of gestation, she underwent repeat amniocentesis which revealed a karyotype of 47,XX,+14 [2]/46,XX [26], consistent with 7% mosaicism for trisomy 14. The parental karyotypes were normal. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed no genomic imbalance. Polymorphic marker analysis excluded uniparental disomy (UPD) 14. Interphase fluorescence in situ hybridization (FISH) analysis on 104 uncultured amniocytes detected no trisomy 14 cell. At 35 weeks of gestation, a 2315-g phenotypically normal baby was delivered. The umbilical cord and placenta had the karyotype of 46, XX (40/40 cells). aCGH analysis on the DNA extracted from peripheral blood and buccal mucosal cells at the age of three months revealed no genomic imbalance. The neonate was normal in phenotype and development during postnatal follow-ups., Conclusions: Low-level mosaic trisomy 14 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 14 cell line and a favorable fetal outcome., Competing Interests: Declaration of competing interest The author has no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Objective: We present mosaic distal 13q duplication due to mosaic unbalanced translocation 46,XY,der(14)t(13;14)(q32.2;p13)/46,XY at amniocentesis in a pregnancy associated with a favorable fetal outcome., Case Report: A 37-year-old, gravida 2, para 0, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, add(14) (p13)[17]/46,XY[13] (56.6% mosaicism). Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed arr 13q32.2q34 × 2∼3, consistent with 45% mosaicism for distal 13q duplication. Repeat amniocentesis at 24 weeks of gestation revealed a karyotype of 46,XY,der(14)t(13;14)(q32.2;p13)[14]/46,XY[16] (46.6% mosaicism). The parental karyotypes were normal. aCGH analysis on the DNA extracted from uncultured amniocytes revealed arr 13q32.2q34 × 2.38, consistent with 30-40% mosaicism for distal 13q duplication. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes detected 22.8% (23/101 cells) mosaicism for distal 13q duplication. Prenatal ultrasound findings were unremarkable. At 39 weeks of gestation, a 3616-g phenotypically normal baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 46,XY,der(14)t(13;14)(q32.2;p13)[20]/46,XY[20] (50% mosaicism), 46,XY,der(14)t(13;14)(q32.2;p13)[14]/46,XY[26] (35% mosaicism) and 46,XY (40/40 cells) (0% mosaicism), respectively. When follow-ups at the age of 4½ months and the age of one year, the peripheral blood had the karyotype of 46,XY,der(14)t(13;14)(q32.2;p13)[18]/46,XY[22] (45% mosaicism). Interphase FISH analysis on buccal mucosal cells at the age of 4½ months revealed 2.7% (3/110 cells) mosaicism for distal 13q duplication, compared with 1% (1/100 cells) in the normal control. The neonate was normal in phenotype and development., Conclusions: Mosaic unbalanced translocation at amniocentesis can be associated with a favorable fetal outcome, perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes., Competing Interests: Declaration of competing interest The author has no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Background:  With the success of free autologous breast reconstruction, the abdominal donor site is now an important consideration, especially in patients of childbearing age. In our institution, there are increasing patients who have successfully undergone the deep inferior epigastric artery perforator (DIEP) flap despite previous pregnancy. This study aims to answer questions on the effect of the donor site on pregnancy and vice versa., Methods:  A retrospective cohort study was conducted to identify breast cancer patients who received a free DIEP flap for breast reconstruction from January 2018 to August 2020. Patients were allocated to two groups according to whether they had prior pregnancies with successful deliveries. Demographics, flap-related parameters, surgical outcomes on breast and abdomen, and patient-reported outcome (Breast-Q questionnaire) were analyzed. Patients were excluded if follow-up time was less than 1 year, or if there was incomplete medical records or Breast-Q replies., Results:  Ninety-nine of 116 patients had had successful pregnancies with delivery, 17 of them remained nulliparous. No statistically significant differences existed between groups regarding demographic data, flap-related parameters, surgical outcomes on breast and abdomen. Nulliparous patients exhibited significantly lower score in physical well-being in the abdomen domain compared with delivery-experienced patients (62.1 vs. 73.4, p  = 0.025). Significantly, nulliparous patients felt more tightness and pulling of the abdominal wall than the delivery-experienced patients (2.9 vs. 3.7; p  = 0.05 and 3.5 vs. 4.0; p  = 0.04)., Conclusion:  Free DIEP flap can be transferred safely in nulliparous patients despite a slight increase in abdominal tightness and abdominal pulling. Precise flap design and surgical approaches may help to minimize the abdominal discomfort especially on young, normal body mass index, and nonchildbearing patients., Competing Interests: None declared., (Thieme. All rights reserved.)

This study was to investigate effects of different phytogenic feed additives (PFA) in grower finishing pigs with stressed by high stocking density. A total of 84 growing pigs ([Landrace × Yorkshire] × Duroc) with initial body weight (BW) of 28.23 ± 0.21 kg were used for 10 weeks (4 replicate pens with 3 pigs per pen). The dietary treatment consisted of basal diets in animal welfare density (positive control [PC]), basal diet in high stocking density (negative control [NC]), NC + 0.04% bitter citrus extract (PT1), NC + 0.01% microencapsulated blend of thymol & carvacrol (PT2), NC + 0.10% mixture of 40% bitter citrus extract and 10% microencapsulated blend of thymol and carvacrol (PT3), NC + 0.04% premixture of grape seed and grape marc extract, green tea and hops (PT4), and NC + 0.10% fenugreek seed powder (PT5). The reduction of space allowance significantly decreased ( p < 0.05) growth performance (average daily gain, average daily feed intake, feed efficiency) and nutrient digestibility (dry matter, crude protein). Also, the fecal score of NC group increased ( p < 0.05) compared with other groups. In blood profiles, lymphocyte decreased ( p < 0.05), and neutrophil, cortisol, TNF-α increased ( p < 0.05) when pigs were in high stocking density. Basic behaviors (feed intake, standing, lying) were inactive ( p < 0.05) and singularity behavior (biting) were increased ( p < 0.05) under high stocking density. However, PFA groups alleviated the negative effects such as reducing growth performance, nutrient digestibility, increasing stress indicators in blood and animal behavior. In conclusion, PFA groups improved the health of pigs with stressed by high stocking density and PT3 is the most effective., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2024 Korean Society of Animal Science and Technology.)

This study investigates the effectiveness of photobiomodulation therapy (PBMT) in treating chronic high-frequency tinnitus with the TINI device, a near-infrared (830 nm) laser. The study includes preliminary animal experiments with 28 mice and a randomized controlled trial with 56 participants to examine the functional and molecular changes in the auditory system that PBMT may cause. The animal model used sodium salicylate to induce tinnitus, followed by PBMT, which showed promising reductions in the behavioral evidence of tinnitus and a reversal of tinnitus-associated upregulation of vesicular glutamate transporters 2 expression in the ipsilateral dorsal cochlear nucleus (p < 0.05). In the clinical trial, participants with chronic high-frequency tinnitus received trans-tympanic application of the TINI device. The results did not show a significant difference in tinnitus score at the final time point when compared to the sham group. However, questionnaires revealed significant improvements in tinnitus symptoms and psychological outcomes following treatment with the TINI device compared to before treatment (p < 0.05). These findings suggest that while PBMT has potential benefits, its clinical effectiveness may be unclear due to its complex nature and interaction with other conditions. Further research is required to optimize treatment parameters and gain a complete understanding of the therapeutic potential of PBMT in managing tinnitus., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

The ability to jet a wide variety of materials consistently from print heads remains a key technical challenge for inkjet-based additive manufacturing processes. Drop watching is the most direct method for testing new inks and print head designs but such experiments are also resource consuming. In this work, a data-efficient machine learning technique called active learning is used to construct detailed jettability diagrams that identify complex regions corresponding to " no jetting ," " jetting ," and " desired jetting ," rather than only individually sampled points. Crucially, our active learning method has resolved challenges with model selection that previously limited the accuracy of active learning in practical settings with very small experimental budgets. In addition, the key " desired jetting " zone may be quite small which is a challenge for initializing active learning. We leverage the physical intuition that the " desired jetting " zone tends to exist between the " jetting" and " no jetting" zone, to improve the performance of this highly imbalanced classification problem by performing two binary classifications in sequence. The first binary classification aims to map out the " jetting " zone versus the "no jetting" zone, while the second binary classification targets identifying the " desired jetting" zone with primary drops only. Our experiments use a stroboscopic drop watcher to visualize the jetting behavior of two fluids from a piezoelectric print head with different jetting waveforms. The results obtained from active learning were compared to a grid search method, which involves running more than 200 experiments for each fluid. The active learning method significantly reduces the number of experiments by 80% while achieving a test accuracy of more than 95% in the "jetting" zone prediction for the test fluids. The ability to construct these jettability diagrams will further accelerate new ink and print head developments., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

Prostate cancer (PCa) is a multifactorial disease influenced by genetic, environmental, and immunological factors. Genetic polymorphisms in the interleukin-10 ( IL-10 ) gene have been implicated in PCa susceptibility, development, and progression. This study aims to assess the contributions of three IL-10 promoter single nucleotide polymorphisms (SNPs), A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872), to the risk of PCa in Taiwan. The three IL-10 genotypes were determined using PCR-RFLP methodology and were evaluated for their contributions to PCa risk among 218 PCa patients and 436 non-PCa controls. None of the three IL-10 SNPs were significantly associated with the risks of PCa ( p all > 0.05) in the overall analyses. However, the GG at rs1800896 combined with smoking behavior was found to significantly increase the risk of PCa by 3.90-fold (95% confidence interval [95% CI] = 1.28-11.89, p = 0.0231). In addition, the rs1800896 AG and GGs were found to be correlated with the late stages of PCa (odds ratio [OR] = 1.90 and 6.42, 95% CI = 1.05-3.45 and 2.30-17.89, p = 0.0452 and 0.0003, respectively). The IL-10 promoter SNP, A-1082G (rs1800896), might be a risk factor for PCa development among smokers and those at late stages of the disease. These findings should be validated in larger and more diverse populations.

Anti-cluster of differentiation (CD) 3 × α programmed death-ligand 1 (PD-L1) bispecific T-cell engager (BsTE)-bound T-cells (BsTE:T) are a promising new cancer treatment agent. However, the mechanisms of action of bispecific antibody-armed activated T-cells are poorly understood. Therefore, this study aimed to investigate the anti-tumor mechanism and efficacy of BsTE:T. The BsTE:T migration was assessed in vivo and in vitro using syngeneic and xenogeneic tumor models, flow cytometry, immunofluorescence staining, transwell migration assays, microfluidic chips, Exo View R100, western blotting, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technology. In murine B16 melanoma, MC38 colon cancer, and human multiple myeloma cells, BsTE:T exhibited superior tumor elimination relative to that of T-cells or BsTE alone. Moreover, BsTE:T migration into tumors was significantly enhanced owing to the presence of PD-L1 in tumor cells and secretion of PD-L1-containing exosomes. Furthermore, increased infiltration of CD44 high CD62L low effector memory CD8 + T-cells into tumors was closely associated with the anti-tumor effect of BsTE:T. Therefore, BsTE:T is an innovative potential anti-tumor therapy, and exosomal PD-L1 plays a crucial role both in vitro and in vivo in the anti-tumor activity of BsTE:T., (© 2024. The Author(s).)

Background: Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages., Methods: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression., Results: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations., Conclusions: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Importance: Acetaminophen (paracetamol) has many pharmacological effects that might be beneficial in sepsis, including inhibition of cell-free hemoglobin-induced oxidation of lipids and other substrates., Objective: To determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo., Design, Setting, and Participants: Phase 2b randomized, double-blind, clinical trial conducted from October 2021 to April 2023 with 90-day follow-up. Adults with sepsis and respiratory or circulatory organ dysfunction were enrolled in the emergency department or intensive care unit of 40 US academic hospitals within 36 hours of presentation., Intervention: Patients were randomized to 1 g of acetaminophen intravenously every 6 hours or placebo for 5 days., Main Outcome and Measures: The primary end point was days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) to day 28. Treatment effect modification was evaluated for acetaminophen by prerandomization plasma cell-free hemoglobin level higher than 10 mg/dL., Results: Of 447 patients enrolled (mean age, 64 [SD, 15] years, 51% female, mean Sequential Organ Failure Assessment [SOFA] score, 5.4 [SD, 2.5]), 227 were randomized to acetaminophen and 220 to placebo. Acetaminophen was safe with no difference in liver enzymes, hypotension, or fluid balance between treatment arms. Days alive and free of organ support to day 28 were not meaningfully different for acetaminophen (20.2 days; 95% CI, 18.8 to 21.6) vs placebo (19.6 days; 95% CI, 18.2 to 21.0; P = .56; difference, 0.6; 95% CI, -1.4 to 2.6). Among 15 secondary outcomes, total, respiratory, and coagulation SOFA scores were significantly lower on days 2 through 4 in the acetaminophen arm as was the rate of development of acute respiratory distress syndrome within 7 days (2.2% vs 8.5% acetaminophen vs placebo; P = .01; difference, -6.3; 95% CI, -10.8 to -1.8). There was no significant interaction between cell-free hemoglobin levels and acetaminophen., Conclusions and Relevance: Intravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill sepsis patients., Trial Registration: ClinicalTrials.gov Identifier: NCT04291508.

Background: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH)., Methods: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-μg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1-3 months., Results: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-μg mRNA-1273, 467 (32.8%) 50-μg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm 3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04-0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09-0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68-5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10-0.41; reference, 100-μg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine)., Conclusions: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-μg mRNA-1273 could generate a higher antibody response than with 50-μg mRNA-1273 and BNT162b2 vaccine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Sterols have long been associated with diverse fields, such as cancer treatment, drug development, and plant growth; however, their underlying mechanisms and functions remain enigmatic. Here, we unveil a critical role played by a GmNF-YC9-mediated CCAAT-box transcription complex in modulating the steroid metabolism pathway within soybeans. Specifically, this complex directly activates squalene monooxygenase (GmSQE1), which is a rate-limiting enzyme in steroid synthesis. Our findings demonstrate that overexpression of either GmNF-YC9 or GmSQE1 significantly enhances soybean stress tolerance, while the inhibition of SQE weakens this tolerance. Field experiments conducted over two seasons further reveal increased yields per plant in both GmNF-YC9 and GmSQE1 overexpressing plants under drought stress conditions. This enhanced stress tolerance is attributed to the reduction of abiotic stress-induced cell oxidative damage. Transcriptome and metabolome analyses shed light on the upregulation of multiple sterol compounds, including fucosterol and soyasaponin II, in GmNF-YC9 and GmSQE1 overexpressing soybean plants under stress conditions. Intriguingly, the application of soybean steroids, including fucosterol and soyasaponin II, significantly improves drought tolerance in soybean, wheat, foxtail millet, and maize. These findings underscore the pivotal role of soybean steroids in countering oxidative stress in plants and offer a new research strategy for enhancing crop stress tolerance and quality from gene regulation to chemical intervention., (© 2024 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Background: Mycoplasma genitalium is an emerging etiology of sexually transmitted infections (STIs) with increasing resistance to antimicrobials. Surveillance on the epidemiology of M. genitalium infection and antimicrobial resistance is warranted., Methods: Between September 2021 and August 2023, people with HIV (PWH) and people without HIV (PWoH) at risk of STIs were screened for M. genitalium infection using a multiplex polymerase-chain-reaction assay of specimens collected from the rectum, urethra, oral cavity, and vagina. The prevalences of resistance-associated mutations (RAMs) of M. genitalium to fluoroquinolones, macrolides, and tetracycline were investigated., Results: During the 2-year study period, 1021 participants were enrolled, including 531 PWH and 490 PWoH. Overall, 83 (8.1%) and 34 (7.6%) participants had M. genitalium infection at baseline and during follow-up, respectively, with the rectum being the most common site of detection (61.5%). With the first course of antimicrobial treatment, 27 of 63 (42.9%) participants with M. genitalium infection were cured during follow-up, including 24 of 58 (41.4%) who received doxycycline monotherapy. The prevalence of RAMs to macrolides, fluoroquinolones, and tetracyclines at baseline were 24.3%, 22.4%, and 7.9%, respectively. Though PWH had more M. genitalium infection (10.2% vs 5.9%, p = 0.01), a higher rate of RAMs to macrolides (41.0% vs 14.7%, p < 0.01) was found in PWoH., Conclusions: Among high-risk populations, the prevalence of M. genitalium infection was 8.1%. The overall genotypic resistance of M. genitalium to macrolides and fluoroquinolones was moderately high in Taiwan. Detection of M. genitalium infection and antimicrobial resistance is warranted to ensure resistance-guided antimicrobial treatments to be administered., Competing Interests: Declaration of competing interest The authors declare that there were no conflicts of interest. This research received grant from National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan (NTUHYL.112.HC001)., (Copyright © 2024. Published by Elsevier B.V.)

Background: No consensus has been reached regarding the efficacy of indirect decompression through oblique lumbar interbody fusion (OLIF) in severe lumbar spinal stenosis (LSS). This study investigated the impact of preoperative magnetic resonance imaging (MRI)-based grading of central and foraminal stenosis on OLIF outcomes in LSS patients and identified risk factors for postoperative clinical dissatisfaction. Methods: We retrospectively reviewed LSS patients who underwent OLIF with a minimum 1-year follow-up. Clinical scores obtained preoperatively and at 3, 6, 12, and 24 months postoperatively were analyzed using the substantial clinical benefit (SCB) framework. The severity of central and foraminal stenosis in the initial MRI was assessed through qualitative grading systems. Results: Among the 145 patients, with a mean follow-up of 33.7 months, those with severe central stenosis showed a significantly higher proportion of patients achieving SCB in the visual analog scale for leg pain (94.5% versus 83.1%; p = 0.044) at one year postoperatively than those without. However, those with severe foraminal stenosis showed significantly higher Oswestry Disability Index (ODI) scores ( p = 0.024), and lower walking ability scores in the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) ( p = 0.004) at one year postoperatively than those without. The presence of a foraminal osteophyte of the superior articular process (SAP) was a significant risk factor responsible for not achieving SCB in ODI and walking ability in JOABPEQ at one year postoperatively (odds ratio: 0.20 and 0.22, respectively). Conclusions: After OLIF, patients with severe central stenosis showed clinical outcomes comparable to those without. The improvement in ODI and walking ability in JOABPEQ was limited in patients with severe foraminal stenosis. Surgeons should consider direct decompression in cases with the presence of foraminal osteophytes of SAP.

This study investigated the effects of lairage conditions on the welfare and meat quality of pigs during lairage periods. A total of 3070 finishing pigs were assigned to one of six groups arranged in two trials in a 2 × 3 factorial design according to the illuminance (under 40 lux (LX), over 40 lux (HX)) and stocking density (low density (LD), higher than 0.83 m 2 /100 kg; normal density (ND), 0.50-0.83 m 2 /100 kg; high density (HD), lower than 0.50 m 2 /100 kg) with high temperature (HT), higher than 24 °C; low temperature (LT), lower than 10 °C. Pigs stocked with HD showed lower aggression behavior and overlap behavior than those stocked with LD at LT. Pigs stocked with HD showed higher standing, sitting, and aggression behavior than those stocked with LD at HT. Pigs stocked with HD showed higher pH than those stocked with LD at LT. At HT, pigs stocked with LD showed higher pH, WHC, DL, and CL than those stocked with HD. At LT, pigs stocked with LD showed higher cortisol levels than those stocked with HD. However, pigs stocked with LD showed lower cortisol levels than those stocked with HD at HT. Based on the obtained results, stocking of too-high (lower than 0.50 m 2 /100 kg) density at HT and stocking of too-low (higher than 0.83 m 2 /100 kg) density at LT are generally not good for meat quality and animal welfare.

Background/Objectives : This study aimed to identify the unique characteristics of neurogenic bladders and associated symptoms in patients with cervical or thoracic myelopathy using clinical surveys and urodynamic studies (UDSs). Methods : Patients with degenerative cervical (DCM) or thoracic (DTM) myelopathy and lower urinary tract symptoms (LUTSs) scheduled for decompressive surgery were prospectively enrolled. A UDS was performed one day preceding surgery to evaluate the preoperative urological function. Subjective symptoms were evaluated using the International Prostate Symptom Score (IPSS) and the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire before surgery and one year postoperatively. Results : Sixty-two patients (DCM: 50, DTM: 12) with a mean age of 63.2 years (men: 30, women: 32) were enrolled. The UDS revealed that 5 (8.1%) patients, all with DCM, exhibited completely normal UDS results, and the remaining 57 had at least one abnormal finding. Based on the International Continence Society classification, an underactive bladder was significantly more common in patients with DTM compared to patients with DCM (75.0% vs. 18.0%, p < 0.001). The results of the questionnaire showed that the voiding symptom IPSS were significantly worse, preoperatively, in patients with DTM (5.0 ± 4.4 [DCM] vs. 8.7 ± 4.5 [DTM]; p = 0.013). One year postoperatively, the IPSS grade of 24.0% of patients with DCM improved, whereas only one (8.3%) patient with DTM showed improvement. Conclusions : Patients with DTM reported worse voiding symptoms and exhibited more underactive bladders on UDS than patients with DCM before decompression. One year postoperatively, more patients with DCM showed subjective improvements in urinary function than those with DTM.

The present study found that using viral filters at the proximal end of a spirometry and CPET test circuit did not significantly alter the test results, with the exception of a marginal decrease noted in peak work rate https://bit.ly/3Vkew95., Competing Interests: Conflict of interests: All authors have no conflicts., (Copyright ©The authors 2024.)

Critical loads (CLs) are frequently used to quantify terrestrial ecosystem impacts from nitrogen (N) deposition using ecological responses such as the growth and mortality of tree species. Typically, CLs are reported as a single value, with uncertainty, for an indicator across a species' entire range. Mediating factors such as climate and soil conditions can influence species' sensitivity to N, but the magnitudes of these effects are rarely calculated explicitly. Here, we quantify the spatial variability and estimation error in N CLs for the growth and survival of 10 different tree species while accounting for key environmental factors that mediate species sensitivity to N (e.g., soil characteristics). We used a bootstrapped machine learning approach to determine the level of N deposition at which a 1% decrease occurs in growth rate or survival probability at forest plot locations across the United States. We found minimal differences (<5 kg N ha -1 year -1 ) when comparing a single species' CLs across climatic regimes but found considerable variability in species' local N CLs (>8.5 kg N ha -1 year -1 ) within these regimes. We also evaluated the most important factors for predicting tree growth rates and mortality and found that climate, competition, and air pollution generally have the greatest influence on growth rates and survival probability. Lastly, we developed a new probability of exceedance metric for each species and found high likelihoods of exceedance across large portions (46%) of some species' ranges. Our analysis demonstrates that machine learning approaches provide a unique capability to: (1) quantify mediating factor influences on N sensitivity of trees, (2) estimate the error in local N CL estimates, and (3) generate localized N CLs with probabilities of exceedance for tree species., Competing Interests: CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest.

Osteoporosis is a common condition that can lead to fractures, mobility issues, and death. Although dual-energy X-ray absorptiometry (DXA) is the gold standard for osteoporosis, it is expensive and not widely available. In contrast, kidney-ureter-bladder (KUB) radiographs are inexpensive and frequently ordered in clinical practice. Thus, it is a potential screening tool for osteoporosis. In this study, we explored the possibility of predicting the bone mineral density (BMD) and classifying high-risk patient groups using KUB radiographs. We proposed DeepDXA-KUB, a deep learning model that predicts the BMD values of the left hip and lumbar vertebrae from an input KUB image. The datasets were obtained from Taiwanese medical centers between 2006 and 2019, using 8913 pairs of KUB radiographs and DXA examinations performed within 6 months. The images were randomly divided into training and validation sets in a 4:1 ratio. To evaluate the model's performance, we computed a confusion matrix and evaluated the sensitivity, specificity, accuracy, precision, positive predictive value, negative predictive value, F1 score, and area under the receiver operating curve (AUROC). Moderate correlations were observed between the predicted and DXA-measured BMD values, with a correlation coefficient of 0.858 for the lumbar vertebrae and 0.87 for the left hip. The model demonstrated an osteoporosis detection accuracy, sensitivity, and specificity of 84.7 %, 81.6 %, and 86.6 % for the lumbar vertebrae and 84.2 %, 91.2 %, and 81 % for the left hip, respectively. The AUROC was 0.939 for the lumbar vertebrae and 0.947 for the left hip, indicating a satisfactory performance in osteoporosis screening. The present study is the first to develop a deep learning model based on KUB radiographs to predict lumbar spine and femoral BMD. Our model demonstrated a promising correlation between the predicted and DXA-measured BMD in both the lumbar vertebrae and hip, showing great potential for the opportunistic screening of osteoporosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Accurate detection of the levator scapulae muscle is critical for effective diagnostic and therapeutic interventions. The commonly used surface anatomy approach has not been validated and is less accurate than ultrasound-guided techniques. Therefore, we determined the needle insertion point for the levator scapulae using a new technique based on the anatomy of the scapula. This investigation used 15 fresh-frozen cadavers to explore the relationship between the acromial angle and medial tip of the scapular spine (O) of the scapular spine. Based on the x-axis (the distance [L] from Point O to point acromial angle) and the y-axis perpendicular to the x-axis passing through Point O, the barycentric coordinates were determined through the intersections of each axis and the superior angle of the scapula with the levator scapulae. Various ratios involving the established distance L) were ascertained, we compared the measurements and ratios between the male and female groups, and the accuracy of the new technique was compared with the conventional technique. The optimal site of the new technique was within 6 to 7% of distance L on the x-axis and 42 to 44% of distance L on the y-axis. This technique was significantly more accurate than the conventional technique (P = .006). Although ultrasound allows for accurate injections via real-time visualization, its unavailability in some cases highlights the importance of understanding surface anatomy landmarks. Our new technique, based on the anatomy of the scapula and relative measurements, is more accurate than the conventional technique. This should enable more precise detection of the levator scapulae for accurate and efficient diagnostic and therapeutic procedures., Competing Interests: Y-SN and JIL contributed equally to this work.The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Medium-entropy alloys (MEAs) have attracted considerable attention in recent decades due to their exceptional material properties and design flexibility. In this study, lightweight and non-equiatomic MEAs with low density (~5 g/cm 3 ), high strength (yield strength: 1200 MPa), and high ductility (plastic deformation: ≧10%) were explored. We fine-tuned a previously developed Ti-rich MEA by microalloying it with small amounts of Ni (reducing the atomic radius and increasing the elastic modulus) through solid solution strengthening to achieve a series of MEAs with enhanced mechanical properties. Among the prepared MEAs, Ti65Ni1 and Ti65Ni3 exhibited optimal properties in terms of the balance between strength and ductility. Furthermore, the Ti65Ni3 MEA was subjected to thermo-mechanical treatment (TMT) followed by cold rolling 70% (CR70) and cold rolling 85% (CR85). Subsequently, the processed samples were rapidly annealed at 743 °C, 770 °C, 817 °C, and 889 °C at a heating rate of 15 °C/s. X-ray diffraction analysis revealed that the MEA could retain its single-body-centered cubic solid solution structure after TMT. Additionally, the tensile testing results revealed that increasing the annealing temperature led to a decrease in yield strength and an increase in ductility. Notably, the Ti65Ni3 MEA sample that was subjected to CR70 and CR85 processing and annealed for 30 s exhibited high yield strength (>1250 MPa) and ductility (>13%). In particular, the Ti65Ni3 MEA subjected to CR85 exhibited a specific yield strength of 264 MPa·cm 3 /g, specific tensile strength of 300 MPa·cm 3 /g, and ductility of >13%.

Background: The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain., Methods: We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians' decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days., Results: A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97-1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94-1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12-1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02-1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01-1.98)., Conclusion: An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19., (Copyright © 2024. Published by Elsevier B.V.)

This review comprehensively examines the evolution and current state of interbody cage technology for lumbar interbody fusion (LIF). This review highlights the biomechanical and clinical implications of the transition from traditional static cage designs to advanced expandable variants for spinal surgery. The review begins by exploring the early developments in cage materials, highlighting the roles of titanium and polyetheretherketone in the advancement of LIF techniques. This review also discusses the strengths and limitations of these materials, leading to innovations in surface modifications and the introduction of novel materials, such as tantalum, as alternative materials. Advancements in three-dimensional printing and surface modification technologies form a significant part of this review, emphasizing the role of these technologies in enhancing the biomechanical compatibility and osseointegration of interbody cages. In addition, this review explores the increase in biodegradable and composite materials such as polylactic acid and polycaprolactone, addressing their potential to mitigate long-term implant-related complications. A critical evaluation of static and expandable cages is presented, including their respective clinical and radiological outcomes. While static cages have been a mainstay of LIF, expandable cages are noted for their adaptability to the patient's anatomy, reducing complications such as cage subsidence. However, this review highlights the ongoing debate and the lack of conclusive evidence regarding the superiority of either cage type in terms of clinical outcomes. Finally, this review proposes future directions for cage technology, focusing on the integration of bioactive substances and multifunctional coatings and the development of patient-specific implants. These advancements aim to further enhance the efficacy, safety, and personalized approach of spinal fusion surgeries. Moreover, this review offers a nuanced understanding of the evolving landscape of cage technology in LIF and provides insights into current practices and future possibilities in spinal surgery.

With the rapid growth of interest in and use of large language models (LLMs) across various industries, we are facing some crucial and profound ethical concerns, especially in the medical field. The unique technical architecture and purported emergent abilities of LLMs differentiate them substantially from other artificial intelligence (AI) models and natural language processing techniques used, necessitating a nuanced understanding of LLM ethics. In this Viewpoint, we highlight ethical concerns stemming from the perspectives of users, developers, and regulators, notably focusing on data privacy and rights of use, data provenance, intellectual property contamination, and broad applications and plasticity of LLMs. A comprehensive framework and mitigating strategies will be imperative for the responsible integration of LLMs into medical practice, ensuring alignment with ethical principles and safeguarding against potential societal risks., Competing Interests: Declaration of interests DSWT holds patents on a deep-learning system for the detection of retinal diseases. AJB is a cofounder and consultant for Personalis and NuMedii; is a consultant to Mango Tree Corporation; has previously been a consultant for Samsung, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, and Merck, and Roche; is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Meta (Facebook), Alphabet (Google), Microsoft, Amazon, Snap, 10x Genomics, Illumina, Regeneron, Sanofi, Pfizer, Royalty Pharma, Moderna, Sutro, Doximity, BioNtech, Invitae, Pacific Biosciences, Editas Medicine, Nuna Health, Assay Depot, and Vet24seven, and several other non-health related companies and mutual funds; has received honoraria and travel reimbursement for invited talks from Johnson and Johnson, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, and many academic institutions, medical-specific or disease-specific foundations and associations, and health systems; receives royalty payments through Stanford University for several patents and other disclosures licensed to NuMedii and Personalis; has done research funded by NIH, Peraton (as the prime on an NIH contract), Genentech, Johnson and Johnson, FDA, Robert Wood Johnson Foundation, Leon Lowenstein Foundation, Intervalien Foundation, Priscilla Chan and Mark Zuckerberg, and the Barbara and Gerson Bakar Foundation; and has previously done research funded by the March of Dimes, Juvenile Diabetes Research Foundation, California Governor's Office of Planning and Research, California Institute for Regenerative Medicine, L’Oreal, and Progenity. NL is a scientific advisor to TIIM SG. NHS is a cofounder of Prealize Health (a predictive analytics company) and Atropos Health (an on-demand evidence generation company); receives funding from the Gordon and Betty Moore Foundation for developing virtual model deployments; and is a member of working groups of the Coalition for Health AI (CHAI), a consensus-building organisation providing guidelines for the responsible use of artificial intelligence in health care. JS, through his involvement with the Murdoch Children's Research Institute, receives funding from the Victorian State Government through the Operational Infrastructure Support (OIS) programme. JCLO is supported by grants from the National Medical Research Council Singapore (MOH-CIAINV21nov-001) and AI Singapore OTTIC (AISG2-TC-2022-006). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The causative pathogen of COVID-19, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), utilizes the receptor-binding domain (RBD) of the spike protein to bind to human receptor angiotensin-converting enzyme 2 (ACE2). Further cleavage of spike by human proteases furin, TMPRSS2, and/or cathepsin L facilitates viral entry into the host cells for replication, where the maturation of polyproteins by 3C-like protease (3CL pro ) and papain-like protease (PL pro ) yields functional nonstructural proteins (NSPs) such as RNA-dependent RNA polymerase (RdRp) to synthesize mRNA of structural proteins. By testing the tea polyphenol-related natural products through various assays, we found that the active antivirals prevented SARS-CoV-2 entry by blocking the RBD/ACE2 interaction and inhibiting the relevant human proteases, although some also inhibited the viral enzymes essential for replication. Due to their multitargeting properties, these compounds were often misinterpreted for their antiviral mechanisms. In this study, we provide a systematic protocol to check and clarify their anti-SARS-CoV-2 mechanisms, which should be applicable for all of the antivirals., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Periprosthetic infections caused by Staphylococcus aureus ( S. aureus ) pose unique challenges in orthopedic surgeries, in part due to the bacterium's capacity to invade surrounding bone tissues besides forming recalcitrant biofilms on implant surfaces. We previously developed prophylactic implant coatings for the on-demand release of vancomycin, triggered by the cleavage of an oligonucleotide (Oligo) linker by micrococcal nuclease (MN) secreted by the Gram-positive bacterium, to eradicate S. aureus surrounding the implant in vitro and in vivo. Building upon this coating platform, here we explore the feasibility of extending the on-demand release to ampicillin, a broad-spectrum aminopenicillin β-lactam antibiotic that is more effective than vancomycin in killing Gram-negative bacteria that may accompany S. aureus infections. The amino group of ampicillin was successfully conjugated to the carboxyl end of an MN-sensitive Oligo covalently integrated in a polymethacrylate hydrogel coating applied to titanium alloy pins. The resultant Oligo-Ampicillin hydrogel coating released the β-lactam in the presence of S. aureus and successfully cleared nearby S. aureus in vitro. When the Oligo-Ampicillin-coated pin was delivered to a rat femoral canal inoculated with 1000 cfu S. aureus , it prevented periprosthetic infection with timely on-demand drug release. The clearance of the bacteria from the pin surface as well as surrounding tissue persisted over 3 months, with no local or systemic toxicity observed with the coating. The negatively charged Oligo fragment attached to ampicillin upon cleavage from the coating did diminish the antibiotic's potency against S. aureus and Escherichia coli ( E. coli ) to varying degrees, likely due to electrostatic repulsion by the anionic surfaces of the bacteria. Although the on-demand release of the β-lactam led to adequate killing of S. aureus but not E. coli in the presence of a mixture of the bacteria, strong inhibition of the colonization of the remaining E. coli on hydrogel coating was observed. These findings will inspire considerations of alternative broad-spectrum antibiotics, optimized drug conjugation, and Oligo linker engineering for more effective protection against polymicrobial periprosthetic infections.

Parkinson's disease (PD) is marked by degeneration in the nigrostriatal dopaminergic pathway, affecting motor control via complex changes in the cortico-basal ganglia-thalamic motor network, including the primary motor cortex (M1). The modulation of M1 neuronal activity by dopaminergic inputs, particularly from the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), plays a crucial role in PD pathophysiology. This study investigates how nigrostriatal dopaminergic degeneration influences M1 neuronal activity in rats using in vivo calcium imaging. Histological analysis confirmed dopaminergic lesion severity, with high lesion level rats showing significant motor deficits. Levodopa treatment improved fine motor abilities, particularly in high lesion level rats. Analysis of M1 calcium signals based on dopaminergic lesion severity revealed distinct M1 activity patterns. Animals with low dopaminergic lesion showed increased calcium events, while high lesion level rats exhibited decreased activity, partially restored by levodopa. These findings suggest that M1 activity is more sensitive to transient fluctuations in dopaminergic transmission, rather than to chronic high or low dopaminergic signaling. This study underscores the complex interplay between dopaminergic signaling and M1 neuronal activity in PD symptoms development. Further research integrating behavioral and calcium imaging data can elucidate mechanisms underlying motor deficits and therapeutic responses in PD., Competing Interests: Conflict of Interest The authors declare no competing interests.

Interest in 3D printing has been growing rapidly especially in pharmaceutical industry due to its multiple advantages such as manufacturing versatility, personalization of medicine, scalability, and cost effectiveness. Inkjet based 3D printing gained special attention after FDA's approval of Spritam® manufactured by Aprecia pharmaceuticals in 2015. The precision and printing efficiency of 3D printing is strongly influenced by the dynamics of ink/binder jetting, which further depends on the ink's fluid properties. In this study, Computational Fluid Dynamics (CFD) has been utilized to study the drop formation process during inkjet-based 3D printing for piezoelectric and thermal printhead geometries using Volume of Fluid (VOF) method. To develop the CFD model commercial software ANSYS-Fluent was used. The developed CFD model was experimentally validated using drop watcher setup to record drop progression and drop velocity. During the study, water, Fujifilm model fluid, and Amitriptyline drug solutions were evaluated as the ink solutions. The drop properties such as drop volume, drop diameter, and drop velocity were examined in detail in response to change ink solution properties such as surface tension, viscosity, and density. A good agreement was observed between the experimental and simulation data for drop properties such as drop volume and drop velocity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments., Materials and Methods: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included., Results: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001)., Conclusions: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: To identify the factors associated with a correction of the segmental angle (SA) with a total change greater than 10° in each level following minimally invasive oblique lumbar interbody fusion (MIS-OLIF)., Methods: Patients with lumbar spinal stenosis who underwent single- or two-level MIS-OLIF were reviewed. Segments with adequate correction of the SA >10° after MIS-OLIF in immediate postoperative radiograph were categorized as discontinuous segments (D segments), whereas those without such improvement were assigned as continuous segments (C segments). Clinical and radiological parameters were compared, and multivariate logistic regression analysis was performed to identify factors associated with SA correction >10° after MIS-OLIF., Results: Of 211 segments included, 38 segments (18.0%) were classified as D segments. Compared with C segments, D segments demonstrated a significantly smaller preoperative SA (mean ± standard deviation [SD], - 1.1° ± 6.7° vs. 6.6° ± 6.3°, p < 0.001), larger change of SA (mean ± SD, 13.5° ± 3.4° vs. 3.1° ± 3.9°, p < 0.001), and a higher rate of presence of facet effusion (76.3% vs. 48.6%, p = 0.002). Logistic regression revealed preoperative SA (odds ratio (OR) [95% confidence interval (CI)]:0.733 [0.639-0.840], p < 0.001) and facet effusion (OR [95% CI]:14.054 [1.758-112.377], p = 0.027) as significant predictors for >10° SA correction after MIS-OLIF., Conclusion: Preoperative kyphotic SA and facet effusion can predict SA correction >10° following MIS-OLIF. For patients with lordotic SA and no preoperative facet effusion, supplemental procedures, such as anterior column release or posterior osteotomy, should be prepared for additional lumbar lordosis correction required for remnant global sagittal imbalance after MIS-OLIF., (© 2024. The Author(s).)

The approach of least squares (LSs) has been quite popular and widely adopted for the common linear regression analysis, which can give rise to the solution to an arbitrary critically-, over-, or under-determined system. Such a linear regression analysis can be easily applied for linear estimation and equalization in signal processing for cybernetics. Nonetheless, the current LS approach for linear regression is unfortunately limited to the dimensionality of data, that is, the exact LS solution can involve only a data matrix. As the dimension of data increases and such data need to be represented by a tensor, the corresponding exact tensor-based LS (TLS) solution does not exist due to the lack of a pertinent mathematical framework. Lately, some alternatives such as tensor decomposition and tensor unfolding were proposed to approximate the TLS solutions to the linear regression problems involving tensor data, but these techniques cannot provide the exact or true TLS solution. In this work, we would like to make the first-ever attempt to present a new mathematical framework for facilitating the exact TLS solutions involving tensor data. To demonstrate the applicability of our proposed new scheme, numerical experiments regarding machine learning and robust speech recognition are illustrated and the associated memory and computational complexities are also studied.

Background/aim: Renal cell carcinoma (RCC) presents a formidable clinical challenge due to its aggressive behavior and limited therapeutic options. Matrix metalloproteinase-8 (MMP-8) has recently emerged as a potential biomarker and therapeutic target for various cancers. However, the genetic involvement of MMP-8 in RCC has remained largely obscure. This study aimed to elucidate the role of MMP-8 genotypes in RCC susceptibility., Materials and Methods: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was employed to scrutinize the genotypes of MMP-8 C-799T (rs11225395), Val436Ala (rs34009635), and Lys460Thr (rs35866072) among 118 RCC patients and 590 controls. Furthermore, potential associations between MMP-8 genotypes and age, sex, smoking, alcohol consumption, hypertension, diabetes, and family history status in relation to RCC risk were assessed., Results: No significant disparities in the distribution of MMP-8 rs11225395, rs34009635, and rs35866072 genotypes were observed between the RCC case and control cohorts (p>0.05). Individuals with CT and TT genotypes at MMP-8 rs11225395 exhibited 0.86- and 0.80-fold RCC risks, respectively (OR=0.57-1.31 and 0.42-1.55, p=0.5585 and 0.6228, respectively). Intriguingly, hypertensive individuals carrying the MMP-8 rs11225395 CT or TT genotype demonstrated an elevated risk for RCC compared to those with wild-type CC genotype (p=0.0440). No interactions of MMP-8 genotypes with age, sex, smoking, alcohol consumption, or diabetes status were evident (all p>0.05). No significant association was discerned for MMP-8 rs34009635 or rs35866072 genotypes., Conclusion: MMP-8 genotypes appear to have a modest influence on individual susceptibility to RCC. Hypertensive patients with the CT or TT MMP-8 rs11225395 genotype may have an elevated risk of RCC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for the motor symptoms of Parkinson's disease (PD). While PD is primarily characterized by motor symptoms such as tremor, rigidity, and bradykinesia, it also involves a range of non-motor symptoms, and anxiety is one of the most common. The relationship between PD and anxiety is complex and can be a result of both pathological neural changes and the psychological and emotional impacts of living with a chronic progressive condition. Managing anxiety in PD is critical for improving the patients' quality of life. However, patients undergoing STN DBS can occasionally experience increased anxiety., Methods: This study investigates changes in risk-avoidant behavior following STN DBS in a pre-motor animal model of PD under chronic and acute unilateral high frequency stimulation., Results: No significant changes in risk-avoidant behaviors were observed in rats who underwent STN DBS compared with sham stimulation controls. Chronic stimulation prevented sensitization in the elevated zero maze., Conclusions: These results suggest that unilateral stimulation of the STN may have minimal effects on risk-avoidant behaviors in PD. However, additional research is required to fully understand the mechanisms responsible for changes in anxiety during STN DBS for PD., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Background: High levels of neutrophil extracellular trap (NET) formation or NETosis and autoantibodies are related to poor prognosis and disease severity of COVID-19 patients. Human angiotensin-converting enzyme 2 (ACE2) cross-reactive anti-severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain (SARS-CoV-2 RBD) antibodies (CR Abs) have been reported as one of the sources of anti-ACE2 autoantibodies. However, the pathological implications of CR Abs in NET formation remain unknown., Methods: In this study, we first assessed the presence of CR Abs in the sera of COVID-19 patients with different severity by serological analysis. Sera and purified IgG from CR Abs positive COVID-19 patients as well as a mouse monoclonal Ab (mAb 127) that can recognize both ACE2 and the RBD were tested for their influence on NETosis and the possible mechanisms involved were studied., Results: An association between CR Abs levels and the severity of COVID-19 in 120 patients was found. The CR Abs-positive sera and IgG from severe COVID-19 patients and mAb 127 significantly activated human leukocytes and triggered NETosis, in the presence of RBD. This NETosis, triggered by the coexistence of CR Abs and RBD, activated thrombus-related cells but was abolished when the interaction between CR Abs and ACE2 or Fc receptors was disrupted. We also revealed that CR Abs-induced NETosis was suppressed in the presence of recombinant ACE2 or the Src family kinase inhibitor, dasatinib. Furthermore, we found that COVID-19 vaccination not only reduced COVID-19 severity but also prevented the production of CR Abs after SARS-CoV-2 infection., Conclusions: Our findings provide possible pathogenic effects of CR Abs in exacerbating COVID-19 by enhancing NETosis, highlighting ACE2 and dasatinib as potential treatments, and supporting the benefit of vaccination in reducing disease severity and CR Abs production in COVID-19 patients., (© 2024. The Author(s).)

Objective: Sleep quality is a crucial concern, particularly among youth. The integration of health coaching with question-answering (QA) systems presents the potential to foster behavioural changes and enhance health outcomes. This study proposes a novel human-AI sleep coaching model, combining health coaching by peers and a QA system, and assesses its feasibility and efficacy in improving university students' sleep quality., Methods: In a four-week unblinded pilot randomised controlled trial, 59 university students (mean age: 21.9; 64% males) were randomly assigned to the intervention (health coaching and QA system; n  = 30) or the control conditions (QA system; n  = 29). Outcomes included efficacy of the intervention on sleep quality (Pittsburgh Sleep Quality Index; PSQI), objective and self-reported sleep measures (obtained from Fitbit and sleep diaries) and feasibility of the study procedures and the intervention., Results: Analysis revealed no significant differences in sleep quality (PSQI) between intervention and control groups (adjusted mean difference = -0.51, 95% CI: [-1.55-0.77], p  = 0.40). The intervention group demonstrated significant improvements in Fitbit measures of total sleep time (adjusted mean difference = 32.5, 95% CI: [5.9-59.1], p  = 0.02) and time in bed (adjusted mean difference = 32.3, 95% CI: [2.7-61.9], p  = 0.03) compared to the control group, although other sleep measures were insignificant. Adherence was high, with the majority of the intervention group attending all health coaching sessions. Most participants completed baseline and post-intervention self-report measures, all diary entries, and consistently wore Fitbits during sleep., Conclusions: The proposed model showed improvements in specific sleep measures for university students and the feasibility of the study procedures and intervention. Future research may extend the intervention period to see substantive sleep quality improvements., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Introduction: Angiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. However, developing agents that can simultaneously target ACE2 and AXL remains a formidable task. The natural compound quercetin has been shown to inhibit AXL expression., Materials and Methods: In this study, we employed PLGA nanoparticles to prepare nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These nanoparticles were tested for their abilities to neutralize or inhibit viral infection., Results: Our data showed that nanoparticles encapsulated with quercetin and then coated with ACE2-containing cell membrane inhibited the expression of AXL without causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and were more effective than free quercetin and nanoparticles encapsulated with quercetin at inhibition of pseudo virus and SARS-CoV-2 infection., Conclusions: We have shown that the biomimetic nanoparticles incorporated with both ACE-2 membrane and quercetin showed the most antiviral activity and may be further explored for clinical application., (© 2024. The Author(s).)

Background: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain., Methods: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative control-patients., Results: A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation., Conclusions: During an early 2022-2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure., Competing Interests: Potential conflicts of interest. S. B. reports participating as the DSMB chair for Hamilton Ventilators, outside the submitted work. J. C. reports receiving funding from the National Institutes of Health (NIH) and Department of Defense (DoD), and a travel grant from Fisher-Paykel, outside the submitted work. S. C. reports consulting for PureTech Health in 2021–2022 and Kiniksa Pharmaceuticals in 2022, outside the submitted work. A. D. reports participating on an advisory board for ALung Technologies and being a principal investigator (PI) for the PETAL Network, outside the submitted work. C. G. G. reports consulting fees from Merck and received research support from Campbell Alliance/Syneos Health, NIH, CDC, Food and Drug Administration (FDA), and AHRQ, outside the submitted work. M. N. G. reports receiving grant funding from NIH and AHRQ for research, honorarium for giving Medicine grand rounds at Yale and Washington Healthcare, fees for DSMB for Palm trial and Regeneron trials on monoclonal antibodies, and fees for serving on scientific advisory board for Philips Healthcare on monitoring, outside the submitted work. R. G. reports consulting for Gilead Sciences, Eli Lily, GSK, Janssen, and AbbVie, being on an advisory board for Gilead Sciences, Eli Lily, GlaxoSmithKline (GSK), and AstraZeneca, speaker bureau for Pfizer and AbbVie, and gift-in-kind to institution from Gilead Sciences, outside the submitted work. N. H. reports prior grant support from Sanofi and Quidel, and current funding from Merck, outside the submitted work. A. L. reports being a consultant for Roche on a clinical trial of baloxavir, outside the submitted work. Christopher Mallow reports medical legal consulting, outside the submitted work. I. P. reports receiving grants from NHLBI, NIGMS, and Janssen Pharmaceuticals and institutional support from Regeneron, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Introduction: Computerized simulation (CS) of surgery in virtual reality (VR), augmented reality (AR) and mixed reality (MR) settings are used to teach foundational skills, but its applicability in advanced training is to be determined. This review aims to summarize the types of CS available for laparoscopic colorectal surgery (CRS) and its utility in assessment of proficiency., Methods: A systematic review of CS in laparoscopic CRS was done on PubMed, Embase, Scopus and Cochrane Library databases., Results: Eleven relevant observational studies were identified. The most common procedure simulated was laparoscopic colectomy. Assessment using performance metrics measured by the simulator such as path length moved by laparoscopic tools, procedure time and number of discrete movements had the most consistent differentiating ability between expert and non-expert cohorts. Surgeons fared similarly in proficiency scores in assessment with CS compared to assessment with traditional cadaveric or porcine models., Conclusion: CS of laparoscopic CRS may be used in assessment of proficiency using performance metrics measuring economy of movement. CS may be a viable assessment tool in advanced surgical training, but further studies should assess utility of incorporating it as a formal assessment tool in training programs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making., Objective: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status., Design, Setting, and Participants: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023., Exposures: RSV, SARS-CoV-2, or influenza infection., Main Outcomes and Measures: Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death., Results: Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001)., Conclusions and Relevance: Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.

Background: Therapeutic-dose heparin decreased days requiring organ support in noncritically ill patients hospitalized for COVID-19, but its impact on persistent symptoms or quality of life (QOL) is unclear., Research Question: In the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 ACUTE (ACTIV-4a) trial, was randomization of patients hospitalized for COVID-19 illness to therapeutic-dose vs prophylactic heparin associated with fewer symptoms and better QOL at 90 days?, Study Design and Methods: This was an open-label randomized controlled trial at 34 hospitals in the United States and Spain. A total of 727 noncritically ill patients hospitalized for COVID-19 from September 2020 to June 2021 were randomized to therapeutic-dose vs prophylactic heparin. Only patients with 90-day data on symptoms and QOL were analyzed. We ascertained symptoms and QOL by the EQ-5D-5L at 90-day follow-up in a preplanned analysis for the ACTIV-4a trial. Individual domains assessed by the EQ-5D-5L included mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Univariate and multivariate analyses were performed., Results: Among 571 patients, 288 (50.4%) reported at least one symptom. Among 410 patients, 148 (36.1%) reported moderate to severe impairment in one or more domains of the EQ-5D-5L. The presence of 90-day symptoms was associated with moderate-severe impairment in the EQ-5D-5L domains of mobility (adjusted OR [aOR], 2.37; 95% CI, 1.22-4.59), usual activities (aOR, 3.66; 95% CI, 1.75-7.65), pain (aOR, 2.43; 95% CI, 1.43-4.12), and anxiety (aOR, 4.32; 95% CI, 2.06-9.02), compared with patients reporting no symptoms There were no differences in symptoms or in the overall EQ-5D-5L index score between treatment groups. Therapeutic-dose heparin was associated with less moderate-severe impairment in all physical functioning domains (mobility, self-care, usual activities) but was independently significant only in the self-care domain (aOR, 0.32; 95% CI, 0.11-0.96)., Interpretation: In a randomized controlled trial of hospitalized noncritically ill patients with COVID-19, therapeutic-dose heparin was associated with less severe impairment in the self-care domain of EQ-5D-5L. However, this type of impairment was uncommon, affecting 23 individuals., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04505774; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: Y. Y. G. is the founder and CEO of Sabra Medical, Inc outside the submitted work. J. S. B. received grants from the National Heart, Lung, and Blood Institute and American Heart Association and personal fees from Jannssen and Amgen, outside the submitted work. L. Z. K. received consulting fees from Cerus, Gamma Diagnostics, and University of Maryland, outside the submitted work. P. R. L. received grants from the National Institutes of Health during the conduct of the study. R. D. L. receive consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, Portola, and Sanofi and grants from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi, outside the submitted work. H. R. R. received nonfinancial support from Siemens, Philips, and Abbott Vascular and grants from the National Heart, Lung, and Blood Institute, outside the submitted work. M. D. N. received personal fees from Haemonetics and Takeda, grants from Instrumentation Laboratories and Haemonetics, and serves on the advisory board for and has equity stake in Haima Therapeutics, outside the submitted work. M. N. G. received grants from the National Institutes of Health and the Centers for Disease Control and Prevention, outside the submitted work. None declared (K. H., J. F., S. R. W., V. V., Y. L., S. Y. C., C. C., F. S., M. G., R. M. G., W. N., J. S. A., L. W., A. Z., E. C. G., R. Z., E. L., D. T. H., J. S. H., M. C.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background/purpose: Dental pulp stem cells (DPSCs) exhibit versatile differentiation capabilities, including neural differentiation, prompting the hypothesis that they may be implicated in the neurodevelopment of teeth. This study aimed to explore the temporospatial dynamics between DPSCs and tooth innervation, employing immunofluorescence staining and fluorescent dye injections to investigate the distribution of DPSCs, neural stem cells (NSCs), nerve growth cones, and sensory nerves in developing mouse tooth germs at various stages., Materials and Methods: Immunofluorescence staining targeting CD146, Nestin, and GAP-43, along with the injection of AM1-43 fluorescent dye, were utilized to observe the distribution of DPSCs, NSCs, nerve growth cones, and sensory nerves in mouse tooth germs at different developmental stages., Results: Positive CD146 immunostaining was observed in microvascular endothelial cells and pericytes within and around the tooth germ. The percentage of CD146-positive cells remained consistent between 4-day-old and 8-day-old second molar tooth germs. Conversely, Nestin expression in odontoblasts and their processes decreased in 8-day-old tooth germs compared to 4-day-old ones. Positive immunostaining for GAP-43 and AM1-43 fluorescence revealed the entry of nerve growth cones and sensory nerves into the pulp in 8-day-old tooth germs, while these elements were confined to the dental follicle in 4-day-old germs. No co-localization of CD146-positive DPSCs with nerve growth cones and sensory nerves was observed., Conclusion: DPSCs and NSCs were present in dental pulp tissue before nerves penetrated the pulp. The decline in NSCs after nerve entry suggests a potential role for DPSCs and NSCs in attracting neural growth and/or differentiation within the pulp., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Gastric peroral endoscopic myotomy (G-POME) is an emerging minimally invasive endoscopic technique involving the establishment of a submucosal tunnel around the pyloric sphincter. In 2013, Khashab et al used G-POME for the first time in the treatment of gastroparesis with enhanced therapeutic efficacy, providing a new direction for the treatment of gastroparesis. With the recent and rapid development of G-POME therapy technology, progress has been made in the treatment of gastroparesis and other upper digestive tract diseases, such as congenital hypertrophic pyloric stenosis and gastric sleeve stricture, with G-POME. This article reviews the research progress and future prospects of G-POME for the treatment of upper digestive tract gastrointestinal diseases., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)