UNASSIGNED: The emergence of multidrug-resistant Klebsiella pneumoniae (K. pneumoniae) and the decline of effective antibiotics lead to the urgent need for new antibacterial agents. The aim of this study is to investigate the therapeutic effect of antimicrobial peptides against gentamicin-resistant (RT) K. pneumoniae and to screen effective antimicrobial peptides.
UNASSIGNED: In this study, the RT strains were induced by gradient gentamicin, and the RT strains were selected by detecting the expression levels of efflux pump genes, porin genes, and biofilm formation genes of the strains combined with their effects on the cells. Then the effects of four antimicrobial peptides on the efflux pump activity, biofilm formation level and cell condition after infection were detected to explore the effects of antimicrobial peptides on RT strains. Finally, the RT strain was used to induce a mouse model of pneumonia, and the four antimicrobial peptides were used to treat pneumonia mice for in vivo experiments. The pathological changes in lung tissues in each group were detected to explore the antimicrobial peptide with the most significant effect on the RT strain in vivo.
UNASSIGNED: The results showed that the minimal inhibitory concentrations of the RT strains (strain C and strain I) were significantly higher than those of the wild-type strain, and the expression of efflux pump, porin and biofilm formation genes was significantly increased. The antimicrobial peptides could effectively inhibit the biofilm formation and efflux pump protein function of the RT strains. In addition, the antimicrobial peptides showed promising antibacterial effects both in vitro and in vivo.
UNASSIGNED: Our study provided a theoretical basis for the treatment of gentamicin resistant K. pneumoniae infection with antimicrobial peptides, and found that KLA was significantly superior to LL37, Magainin I, KLA and Dermaseptin (10 μg/mL in cells, 50 μg in mice).

The present retrospective study investigated the clinical features and prognosis of secondary hematological malignancies (SHMs) in patients with sarcoma at Korea Cancer Center Hospital (Seoul, South Korea). Patients who had been diagnosed with SHMs after having received treatment for sarcoma between January 2000 and May 2023 were enrolled. Clinical data were collected from the patients\' medical records. Clinical characteristics were analyzed, including SHM incidence, type and prognosis. Of 2,953 patients with sarcoma, 18 (0.6%) were diagnosed with SHMs. Their median age at the time of sarcoma diagnosis was 39.5 (range, 9-72) years, and 74% (n=14) of these patients were male. The histological features of sarcoma varied, with osteosarcoma diagnosed in nine patients (50%). All patients with sarcoma underwent surgical treatment, and 16 (88.8%) received chemotherapy. The most common type of SHMs was acute myeloid leukemia (n=6; 33.3%), followed by myelodysplastic syndrome (n=5; 27.7%). The median latency period between the sarcoma diagnosis and SHM identification was 30 (range, 11-121) months. A total of 13 (72.2%) patients received treatment for the SHM. The median overall survival after SHM diagnosis was 15.7 (range, 0.4-154.9) months. The incidence of SHMs in sarcoma in the present study was consistent with that reported previously. The presence of SHMs was associated with a poor patient prognosis, especially if treatment for SHMs was not administered.

UNASSIGNED: High-flow nasal cannula (HFNC) is an essential non-invasive oxygen therapy in acute respiratory distress syndrome (ARDS) patients. Despite its wide use, research assessing the knowledge, practice, and barriers to using HFNC among respiratory therapists (RT) is lacking.
UNASSIGNED: A cross-sectional questionnaire was conducted among RTs in Saudi Arabia between December 19, 2022, and July 15, 2023. Data were analyzed as means and standard deviation or frequency and percentages. A Chi-square test was used to compare the differences between groups.
UNASSIGNED: A total of 1001 RTs completed the online survey. Two-thirds of the respondents 659 (65.8%) had received training in using HFNC and 785 (78.4%) had used HFNC in clinical settings. The top conditions for HFNC indication were COVID-19 (78%), post-extubation (65%), and do-not-intubate patients (64%). Participants strongly agreed that helping maintain conversation and eating abilities (32.95%) and improving shortness of breath (34.1%) were advantages of HFNC. Surprisingly, 568 (57%) of RT staff did not follow a protocol for HFNC with ARDS patients. When starting HFNC, 40.2% of the participants started with FiO2 of 61% to 80%. Additionally, high percentages of RT staff started with a flow rate between 30 L/minute and 40 L/minute (40.6%) and a temperature of 37°C (57.7%). When weaning ARDS patients, 482 (48.1%) recommended first reducing gas flow by 5-10 L/minute every two to four hours. Moreover, 549 (54.8%) believed that ARDS patients could be disconnected from HFNC if they achieved a flow rate of <20 L/minute and FiO2 of <35%. Lack of knowledge was the most common challenge concerning HFNC implementation.
UNASSIGNED: The findings revealed nuanced applications marked by significant endorsement in certain clinical scenarios and a lack of protocol adherence, underscoring the need for uniform, evidence-based guidelines and enhanced training for RTs. Addressing these challenges is pivotal to optimizing the benefits of HFNC across varied clinical contexts.

The present study aimed to investigate the value of intravoxel incoherent motion imaging (IVIM) and three-dimensional pulsed continuous arterial spin labeling (ASL) in assessing dynamic changes of the parotid gland in patients with nasopharyngeal carcinoma (NPC) following radiotherapy (RT). A total of 18 patients with NPC who underwent intensity-modulated RT were enrolled in the present study. All patients underwent conventional magnetic resonance imaging, plus IVIM and ASL imaging of the bilateral parotid glands within 2 weeks prior to RT, and 1 week (1W) and 3 months (3M) following RT. Pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (F) and blood flow (BF) were analyzed. D and BF values were significantly increased from pre-RT to 1W post-RT [change rate: Median (IQR), ΔD1W%: 39.28% (38.23%) and ΔBF1W%: 60.84% (54.88%)] and continued to increase from 1W post-RT to 3M post-RT [55.44% (40.56%) and ΔBF%: 120.39% (128.74%)]. In addition, the F value was significantly increased from pre-RT to 1W post-RT, [change rate: Median (IQR), ΔF1W%: 28.13% (44.66%)], and this decreased significantly from 1W post-RT to 3M post-RT. However, no significant differences were observed between pre-RT and 3M post-RT. Results of the present study also demonstrated that the D* value was significantly decreased from pre-RT to 1W post-RT and 3M post-RT [change rate: Median (IQR), ΔD*1w%: -41.86% (51.71%) and ΔD*3M: -29.11% (42.67%)]. No significant difference was observed between the different time intervals post-RT. There was a significant positive correlation between percentage change in ΔBF1W and radiation dose (ρ=0.548, P=0.001). Thus, IVIM-diffusion-weighted imaging and ASL may aid in the detection and prediction of radiation-induced parotid damage in the early stages following RT. They may contribute to further understanding the potential association between damage to the parotid glands and patient-/treatment-related variables, through the assessment of individual microcapillary perfusion and tissue diffusivity.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are an important component of anti-acquired immunodeficiency syndrome treatment regimen. In the present work, with the previously reported compound K-16c as lead, a series of novel 2,4,5-trisubstituted pyrimidine derivatives were designed based on the cocrystal structure of K-16c/RT, with the aim to improve the anti-human immunodeficiency virus type-1 (HIV-1) activities and metabolic stability properties. Compound 11b1 exhibited the most potent antiviral activity against wild-type (WT) and a panel of single mutant HIV-1 strains (EC50  = 2.4-12.4 nM), being superior to or comparable to those of the approved drug etravirine. Meanwhile, 11b1 exhibited moderate cytotoxicity (CC50  = 4.96 μM) and high selectivity index (SI = 1189) toward HIV-1 WT strain. As for HIV-1 RT inhibition test, 11b1 possessed excellent inhibitory potency (IC50  = 0.04 μM) and confirmed its target was RT. Moreover, the molecular dynamics simulation was performed to elucidate the improved drug resistance profiles. Moreover, 11b1 was demonstrated with favorable safety profiles and pharmacokinetic properties in vivo, indicating that 11b1 is a potential anti-HIV-1 drug candidate worthy of further development.

OBJECTIVE: In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in the perioperative setting. This has led to clinical scenarios where radiation therapy (RT) is given concurrently with ICIs. On the other hand, moderate and ultrahypofractionated schedules of RT are being widely adopted in the adjuvant setting, in addition to an increased use of metastasis-directed therapy. Furthermore, RT can modulate the tumor microenvironment and induce a systemic response at nonirradiated sites, an \"abscopal effect.\" The amplification of antitumor immune response is used as the rationale behind the concomitant use of ICIs and RT. To date, there is a lack of literature on the optimal sequence, timing, dose/fractionation schema, and treated RT volumes with ICIs in patients with BC, especially in the era of ultrahypofractionation.
METHODS: We conducted a systematic review to delineate the reported treatment details, safety, and efficacy of combining ICI and RT in patients with BC. PubMed, Embase, and Cochrane CENTRAL were searched between 2014 and 2023. Data were extracted to assess the details of ICIs/RT delivery, safety, and efficacy.
RESULTS: Of the 12 eligible studies, 9 involved patients with metastatic BC. Most studies were phase 1/2, had a small sample size (range, 8-28), and were heterogenous in patient population and reported outcomes. The combination was reported to be safe. We identified 1 study in the perioperative setting, which did a posthoc analysis of safety/efficacy of ICIs in the adjuvant setting with receipt and pattern of RT.
CONCLUSIONS: In conclusion, there are limited data on the dose, timing, fractionation, and volumes of RT in both the adjuvant and metastatic setting in BC. Ongoing/future trials should collect and report such data on RT details, whenever RT is used in combination with ICIs.

In patients with early-stage or recurrent NSCLC who are unable to tolerate surgery, a benefit could derive only from a systemic therapy or another few forms of local therapy. A systematic review was performed to evaluate the feasibility and the effectiveness of radiotherapy combined with local ablative therapies in the treatment of primary and recurrent lung cancer in terms of toxicity profile and local control rate. Six studies featuring a total of 115 patients who met eligibility criteria and 119 lesions were included. Three studies evaluated lung cancer patients with a medically inoperable condition treated with image-guided local ablative therapies followed by radiotherapy: their local control rate (LC) ranged from 75% to 91.7% with only 15 patients (19.4%) reporting local recurrence after combined modality treatment. The other three studies provided a salvage option for patients with locally recurrent NSCLC after RT: the median follow-up period varied from 8.3 to 69.3 months with an LC rate ranging from 50% to 100%. The most common complications were radiation pneumonitis (9.5%) and pneumothorax (29.8%). The proposed intervention appears to be promising in terms of toxicity profile and local control rate. Further prospective studies are need to better delineate combining LTA-RT treatment benefits in this setting.

Following on our recently developed biphenyl-ATDP non-nucleoside reverse transcriptase inhibitor ZLM-66 (SI = 2019.80, S = 1.9 μg/mL), a series of novel heterocycle-substituted ATDP derivatives with significantly improved selectivity and solubility were identified by replacement of the biphenyl moiety of ZLM-66 with heterocyclic group with lower lipophilicity. Evidently, the representative analog 7w in this series exhibited dramatically enhanced selectivity and solubility (SI = 12,497.73, S = 4472 μg/mL) in comparison with ZLM-66 (SI = 2019.80, S = 1.9 μg/mL). This new NNRTI conferred low nanomolar inhibition of wild-type HIV-1 strain and tested mutant strains (K103N, L100I, Y181C, E138K, and K103N + Y181C). The analog also demonstrated favorable safety and pharmacokinetic profiles, as evidenced by its insensitivity to CYP and hERG, lack of mortality and pathological damage, and good oral bioavailability in rats (F = 27.1%). Further development of 7w for HIV therapy will be facilitated by this valuable information.

Owing to their large surface area, two-dimensional (2D) semiconducting nanomaterials have been extensively studied for gas-sensing applications in recent years. In particular, the possibility of operating at room temperature (RT) is desirable for 2D gas sensors because it significantly reduces the power consumption of the sensing device. Furthermore, RT gas sensors are among the first choices for the development of flexible and wearable devices. In this review, we focus on the 2D MXenes used for the realization of RT gas sensors. Hence, pristine, doped, decorated, and composites of MXenes with other semiconductors for gas sensing are discussed. Two-dimensional MXene nanomaterials are discussed, with greater emphasis on the sensing mechanism. MXenes with the ability to work at RT have great potential for practical applications such as flexible and/or wearable gas sensors.

Magnetic resonance imaging (MRI) provides excellent visualization of central nervous system (CNS) tumors due to its superior soft tissue contrast. Magnetic resonance-guided radiotherapy (MRgRT) has historically been limited to use in the initial treatment planning stage due to cost and feasibility. MRI-guided linear accelerators (MRLs) allow clinicians to visualize tumors and organs at risk (OARs) directly before and during treatment, a process known as online MRgRT. This novel system permits adaptive treatment planning based on anatomical changes to ensure accurate dose delivery to the tumor while minimizing unnecessary toxicity to healthy tissue. These advancements are critical to treatment adaptation in the brain and spinal cord, where both preliminary MRI and daily CT guidance have typically had limited benefit. In this narrative review, we investigate the application of online MRgRT in the treatment of various CNS malignancies and any relevant ongoing clinical trials. Imaging of glioblastoma patients has shown significant changes in the gross tumor volume over a standard course of chemoradiotherapy. The use of adaptive online MRgRT in these patients demonstrated reduced target volumes with cavity shrinkage and a resulting reduction in radiation dose to uninvolved tissue. Dosimetric feasibility studies have shown MRL-guided stereotactic radiotherapy (SRT) for intracranial and spine tumors to have potential dosimetric advantages and reduced morbidity compared with conventional linear accelerators. Similarly, dosimetric feasibility studies have shown promise in hippocampal avoidance whole brain radiotherapy (HA-WBRT). Next, we explore the potential of MRL-based multiparametric MRI (mpMRI) and genomically informed radiotherapy to treat CNS disease with cutting-edge precision. Lastly, we explore the challenges of treating CNS malignancies and special limitations MRL systems face.