bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Diameter of Inhibition in Crowded Plates on the in vitro Inhibitory Strength of Potential Antibiotic-Producing Bacteria Isolated from Some Natural Habitats
Authors: Balogun Olasinbo Olumuyiwa , Ugoh Sylvanus Chukwudi , Abioye Olabisi Peter , Oladosu Peters Oluwale
Published: September 2023

Antimicrobial resistance is a global problem, and efforts to replace failing antibiotics are crucial. We investigated the impact of the diameter of inhibition (mm) in crowded plates of potential antibiotic-producing bacteria on their in-vitro inhibitory strength. Our previous research identified 12 potential antibiotic-producing bacteria from natural habitats and obtained their diameters of inhibition in preliminary crowded plates. The potential candidates were further challenged with some pathogenic microbes by the Agar-well diffusion technique to test their strength. The results showed that the diameter of inhibition of the potential antibiotic-producing isolates obtained at the crowded plate technique level was not a predictor of the potency of potential antibiotic-producing bacteria (rs = 0.52, P = 0.08).  In summary, the selection of potent candidate microbes for the development of new antimicrobial compounds against multidrug-resistant pathogens cannot be determined based on the diameter of inhibition in a preliminary investigation using the crowded plate technique. Further studies involving complementary techniques are necessary to determine the best potential candidate organisms for the development of novel antimicrobial compounds.
Overall Survival Among Patients With De Novo Stage IV Metastatic and Distant Metastatic Recurrent Non–Small Cell Lung Cancer
Authors: Su Chloe C. , Wu Julie T. , Choi Eunji , Myall Nathaniel J. , Neal Joel W. , Kurian Allison W. , Stehr Henning , Wood Douglas , Henry Solomon M. , Backhus Leah M. , Leung Ann N. , Wakelee Heather A. , Han Summer S.
Published: September 2023

Importance

Despite recent breakthroughs in therapy, advanced lung cancer still poses a therapeutic challenge. The survival profile of patients with metastatic lung cancer remains poorly understood by metastatic disease type (ie, de novo stage IV vs distant recurrence).

Objective

To evaluate the association of metastatic disease type on overall survival (OS) among patients with non–small cell lung cancer (NSCLC) and to identify potential mechanisms underlying any survival difference.

Design, Setting, and Participants

Cohort study of a national US population based at a tertiary referral center in the San Francisco Bay Area using participant data from the National Lung Screening Trial (NLST) who were enrolled between 2002 and 2004 and followed up for up to 7 years as the primary cohort and patient data from Stanford Healthcare (SHC) for diagnoses between 2009 and 2019 and followed up for up to 13 years as the validation cohort. Participants from NLST with de novo metastatic or distant recurrent NSCLC diagnoses were included. Data were analyzed from January 2021 to March 2023.

Exposures

De novo stage IV vs distant recurrent metastatic disease.

Main Outcomes and Measures

OS after diagnosis of metastatic disease.

Results

The NLST and SHC cohort consisted of 660 and 180 participants, respectively (411 men [62.3%] vs 109 men [60.6%], 602 White participants [91.2%] vs 111 White participants [61.7%], and mean [SD] age of 66.8 [5.5] vs 71.4 [7.9] years at metastasis, respectively). Patients with distant recurrence showed significantly better OS than patients with de novo metastasis (adjusted hazard ratio [aHR], 0.72; 95% CI, 0.60-0.87; P < .001) in NLST, which was replicated in SHC (aHR, 0.64; 95% CI, 0.43-0.96; P = .03). In SHC, patients with de novo metastasis more frequently progressed to the bone (63 patients with de novo metastasis [52.5%] vs 19 patients with distant recurrence [31.7%]) or pleura (40 patients with de novo metastasis [33.3%] vs 8 patients with distant recurrence [13.3%]) than patients with distant recurrence and were primarily detected through symptoms (102 patients [85.0%]) as compared with posttreatment surveillance (47 patients [78.3%]) in the latter. The main finding remained consistent after further adjusting for metastasis sites and detection methods.

Conclusions and Relevance

In this cohort study, patients with distant recurrent NSCLC had significantly better OS than those with de novo disease, and the latter group was associated with characteristics that may affect overall survival. This finding can help inform future clinical trial designs to ensure a balance for baseline patient characteristics.
Deep Learning Empowers the Discovery of Self‐Assembling Peptides with Over 10 Trillion Sequences
Authors: Wang Jiaqi , Liu Zihan , Zhao Shuang , Xu Tengyan , Wang Huaimin , Li Stan Z. , Li Wenbin
Published: September 2023

Self‐assembling of peptides is essential for a variety of biological and medical applications. However, it is challenging to investigate the self‐assembling properties of peptides within the complete sequence space due to the enormous sequence quantities. Here, it is demonstrated that a transformer‐based deep learning model is effective in predicting the aggregation propensity (AP) of peptide systems, even for decapeptide and mixed‐pentapeptide systems with over 10 trillion sequence quantities. Based on the predicted AP values, not only the aggregation laws for designing self‐assembling peptides are derived, but the transferability relation among the APs of pentapeptides, decapeptides, and mixed pentapeptides is also revealed, leading to discoveries of self‐assembling peptides by concatenating or mixing, as consolidated by experiments. This deep learning approach enables speedy, accurate, and thorough search and design of self‐assembling peptides within the complete sequence space of oligopeptides, advancing peptide science by inspiring new biological and medical applications.
Improved Humoral Immunity and Protection against Influenza Virus Infection with a 3d Porous Biomaterial Vaccine
Authors: Miwa Hiromi , Antao Olivia Q. , Kelly‐Scumpia Kindra M. , Baghdasarian Sevana , Mayer Daniel P. , Shang Lily , Sanchez Gina M. , Archang Maani M. , Scumpia Philip O. , Weinstein Jason S , Di Carlo Dino
Published: September 2023

New vaccine platforms that activate humoral immunity and generate neutralizing antibodies are required to combat emerging pathogens, including influenza virus. A slurry of antigen‐loaded hydrogel microparticles that anneal to form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades is demonstrated to enhance humoral immunity. Antigen‐loaded‐microgels elicited a robust cellular humoral immune response, with increased CD4+ T follicular helper (Tfh) cells and prolonged germinal center (GC) B cells comparable to the commonly used adjuvant, aluminum hydroxide (Alum). Increasing the weight fraction of polymer material led to increased material stiffness and antigen‐specific antibody titers superior to Alum. Vaccinating mice with inactivated influenza virus loaded into this more highly cross‐linked formulation elicited a strong antibody response and provided protection against a high dose viral challenge. By tuning physical and chemical properties, adjuvanticity can be enhanced leading to humoral immunity and protection against a pathogen, leveraging two different types of antigenic material: individual protein antigen and inactivated virus. The flexibility of the platform may enable design of new vaccines to enhance innate and adaptive immune cell programming to generate and tune high affinity antibodies, a promising approach to generate long‐lasting immunity.
In Vivo Intra‐Uterine Delivery of TAT‐Fused Cre Recombinase and CRISPR/Cas9 Editing System in Mice Unveil Histopathology of Pten/p53‐Deficient Endometrial Cancers
Authors: Navaridas Raúl , Vidal‐Sabanés Maria , Ruiz‐Mitjana Anna , Altés Gisela , Perramon‐Güell Aida , Yeramian Andree , Egea Joaquim , Encinas Mario , Gatius Sonia , Matias‐Guiu Xavier , Dolcet Xavier
Published: September 2023

Phosphatase and TENsin homolog (Pten) and p53 are two of the most frequently mutated tumor suppressor genes in endometrial cancer. However, the functional consequences and histopathological manifestation of concomitant p53 and Pten loss of function alterations in the development of endometrial cancer is still controversial. Here, it is demonstrated that simultaneous Pten and p53 deletion is sufficient to cause epithelial to mesenchymal transition phenotype in endometrial organoids. By a novel intravaginal delivery method using HIV1 trans‐activator of transcription cell penetrating peptide fused with a Cre recombinase protein (TAT‐Cre), local ablation of both p53 and Pten is achieved specifically in the uterus. These mice developed high‐grade endometrial carcinomas and a high percentage of uterine carcinosarcomas resembling those found in humans. To further demonstrate that carcinosarcomas arise from epithelium, double Pten/p53 deficient epithelial cells are mixed with wild type stromal and myometrial cells and subcutaneously transplanted to Scid mice. All xenotransplants resulted in the development of uterine carcinosarcomas displaying high nuclear pleomorphism and metastatic potential. Accordingly, in vivo CRISPR/Cas9 disruption of Pten and p53 also triggered the development of metastatic carcinosarcomas. The results unfadingly demonstrate that simultaneous deletion of p53 and Pten in endometrial epithelial cells is enough to trigger epithelial to mesenchymal transition that is consistently translated to the formation of uterine carcinosarcomas in vivo.
Optically Programmable Living Microrouter in Vivo
Authors: Liu Xiaoshuai , Wu Huaying , Wu Shuai , Qin Haifeng , Zhang Tiange , Lin Yufeng , Zheng Xianchuang , Li Baojun
Published: September 2023

With high reconfigurability and swarming intelligence, programmable medical micromachines (PMMs) represent a revolution in microrobots for executing complex coordinated tasks, especially for dynamic routing of various targets along their respective routes. However, it is difficult to achieve a biocompatible implantation into the body due to their exogenous building blocks. Herein, a living microrouter based on an organic integration of endogenous red blood cells (RBCs), programmable scanning optical tweezers and flexible optofluidic strategy is reported. By harvesting energy from a designed optical force landscape, five RBCs are optically rotated in a controlled velocity and direction, under which, a specific actuation flow is achieved to exert the well‐defined hydrodynamic forces on various biological targets, thus enabling a selective routing by integrating three successive functions, i.e., dynamic input, inner processing, and controlled output. Benefited from the optofluidic manipulation, various blood cells, such as the platelets and white blood cells, are transported toward the damaged vessel and cell debris for the dynamic hemostasis and targeted clearance, respectively. Moreover, the microrouter enables a precise transport of nanodrugs for active and targeted delivery in a large quantity. The proposed RBC microrouter might provide a biocompatible medical platform for cell separation, drug delivery, and immunotherapy.
Occupational injuries and illnesses among law enforcement officers, 2001−2019: Findings from the Ohio Bureau of Workers' Compensation
Authors: Tiesman Hope M. , Konda Srinivas , Wurzelbacher Steven J. , Naber Steven J. , Attwood Wesley R.
Published: September 2023

Background

Occupational injuries are common among law enforcement officers (LEOs) and can impact an agency's ability to serve communities. Workers' compensation (WC) data are an underutilized source for occupational injury surveillance in the law enforcement field.

Methods

LEOs WC claims from the Ohio Bureau of Workers' Compensation (OHBWC) from 2001 to 2019 were identified based on manual review of the occupation title and injury description. Worker, employer, incident, and injury characteristics were described by claim type—medical‐only (MO) and lost‐time (8 or more days away from work). Data are presented using injury claim counts.

Results

From 2001 to 2019, 50,793 WC claims were identified among Ohio LEOs. Of these, 68% were MO claims (n = 34,622). WC claims significantly decreased over the 19‐year period (p < 0.001). Seventy‐five percent of WC claims were from a LEO with more than one claim and of these, 34% were from a LEO with five or more claims during the study period. Male officers and those aged 25−54 years incurred the highest proportion of total claims (87.8% & 91.8%, respectively). Violence (n = 17,247; 34%), falls/slips/trips (n = 9079; 17.9%), and transportation events (n = 7977; 15.7%) were the leading events. Among the 50,793 claims, there were 79,637 unique clinical diagnosis groups. The most common injury diagnoses were sprains (n = 32,796; 41.2%) followed by contusions (n = 13,529; 17%).

Conclusions

Results can guide the development or improvement of workplace injury prevention strategies for LEOs. Efforts should be focused on better understanding and preventing violent injury events and sprains among LEOs, as well as preventing multiple injury events.
Ultrafluorogenic Monochromophore‐Type BODIPY‐Tetrazine Series for Dual‐Color Bioorthogonal Imaging with a Single Probe
Authors: Kim Dahham , Son Hayoung , Park Seung Bum
Published: September 2023

Various fluorogenic probes utilizing tetrazine (Tz) as a fluorescence quencher and bioorthogonal reaction partner have been extensively studied over the past few decades. Herein, we synthesized a series of boron‐dipyrromethene (BODIPY)‐Tz probes using monochromophoric design strategy for bioorthogonal cellular imaging. The BODIPY‐Tz probes exhibited excellent bicyclo[6.1.0]nonyne (BCN)‐selective fluorogenicity with three‐ to four‐digit‐fold enhancements in fluorescence over a wide range of emission wavelengths, including the far‐red region. Furthermore, we demonstrated the applicability of BODIPY‐Tz probes in bioorthogonal fluorescence imaging of cellular organelles without washing steps. We also elucidated the aromatized pyridazine moiety as the origin of BCN‐selective fluorogenic behavior. Additionally, we discovered that the fluorescence of the trans‐cyclooctene (TCO) adducts was quenched in aqueous media via photoinduced electron transfer (PeT) process. Interestingly, we observed a distinctive recovery of the initially quenched fluorescence of BODIPY‐Tz‐TCO upon exposure to hydrophobic media, accompanied by a significant bathochromic shift of its emission wavelength relative to that exhibited by the corresponding BODIPY‐Tz‐BCN. Leveraging this finding, for the first time, we achieved dual‐color bioorthogonal cellular imaging with a single BODIPY‐Tz probe.
External genitalia phenotypes of a Mab21l1‐null mouse model for cerebellar, ocular, craniofacial, and genital (COFG) syndrome
Authors: Promsut Watcharapon , Yamada Ryuichi , Takami Shohei , Miyazaki Nanae , Uemura Mami , Hiramatsu Ryuji , Takahashi Naoki , Kanai Yoshiakira
Published: September 2023

The cerebellar, ocular, craniofacial, and genital (COFG) syndrome is a human genetic disease that is caused by MAB21L1 mutations. A COFG mouse model with Mab21l1‐null mutation causes severe microphthalmia and fontanelle dysosteogenesis, similar to the symptoms in human patients. One of the typical symptoms is scrotal agenesis in male infants, while male Mab21l1‐null mice show hypoplastic preputial glands, a rodent‐specific derivative of the cranial scrotal fold. However, it is still unclear where and how MAB21Ll acts in the external genitalia in both mice and humans. Here we show that, at the neonatal stage, MAB21L1 expression in the external genitalia was restricted to two mesenchymal cell populations—underneath the scrotal and labial skin and around the preputial and clitoral glands (PG/CG). Morphometric analyses of the Mab21l1−/− pups revealed a significant reduction in the external size of the scrotum, vulva, and CG, as well as PG. In the periglandular region around PG and CG, the periglandular mesenchymal cells showed a drastic reduction in both cell density and immunoreactive signals for several extracellular matrix proteins (e.g., collagen I, fibronectin, and proteoglycans), together with their reduced Ki67‐positive cell proliferation index. In the Mab21l1−/− PG/CG, together with reduced vascularization, the glandular epithelia displayed atrophy with discontinuous basal lamina along the basal surface and defective glycogen accumulation in their cytoplasm. Under a 5‐day organ culture of the isolated PG, the Mab21l1−/− explants showed poor outgrowth and retention of the glandular structure in vitro. However, the addition of exogenous Matrigel could partially rescue such tissue‐autonomous phenotypes, showing glandular morphology similar to that of the wild‐type explants. These findings suggest that MAB21L1+ mesenchymal cells play a crucial role in providing nutrient ECM support for glandular outgrowth and morphogenesis in the peripheral external genitalia.
Constructive alignment: Teaching introductory gross anatomy to sport science students
Authors: Downie Calum , Burke Michael
Published: September 2023

The purpose of this descriptive article was to illustrate the process of using constructive alignment in redesigning an introductory gross anatomy unit that is taught specifically to sports science and physical education students at Victoria University. The unit was redesigned as an intensive learning unit in 2017 as part of a broader university‐wide process. The teaching team decided that the first stage of the constructive alignment process should be necessarily focused on an understanding of the career destinations of graduates from the courses. With this understanding, it became easier to work through the redesign of intended learning objectives, the shift from systemic to regional anatomy changes in content and learning support mechanisms, and alterations to assessment practices. A comparison of student pass rates for the unit from 2018 to 2023 with pass rates in the previous semester‐long version of the unit, suggests optimism about the changes that were made through the constructive alignment process. However, there were a number of other factors that may have contributed to this result, and more research is needed on the specific effectiveness of the changes made during the constructive alignment process before a confident conclusion about the success of the process can be made.
Tauroursodeoxycholic acid protects Schwann cells from high glucose–induced cytotoxicity by targeting NLRP3 to regulate cell migration and pyroptosis
Authors: Wang Qiuyue , Li Wen , Zhang Xiaozhuo , Chung Shuet Ling , Dai Jinling , Jin Zhu
Published: September 2023

Diabetic peripheral neuropathy (DPN) is the most prevalent complication of type 2 diabetes mellitus (T2DM), and it seriously affects the quality of life of patients. Tauroursodeoxycholic acid (TUDCA) is a bile acid that plays a protective role against various diseases. However, the function of TUDCA in DPN progression needs to be elucidated. Hence, this study clarified the action of TUDCA on DPN development and explored its mechanism of action. Fecal samples were collected from 50 patients with T2DM or DPN. Schwann cells induced by high levels were constructed to simulate an uncontrolled diabetic state. Cell viability and migration were measured using the CCK‐8 and wound‐healing assays, respectively. Reactive oxygen species and pyroptosis were detected using flow cytometry. Parabacteroides goldsteinii and Parabacteroides distasonis levels were decreased in the feces of patients with DPN. TUDCA enhanced the viability and migration ability of high glucose‐stimulated Schwann cells. In addition, Schwann cell pyroptosis stimulated by high glucose levels was inhibited by TUDCA. Furthermore, the protective roles of TUDCA in cell viability, migration ability, and pyroptosis of Schwann cells stimulated by high glucose were suppressed by the overexpression of NLRP3. TUDCA enhanced cell viability and migration and suppressed pyroptosis in Schwann cells stimulated by high glucose levels by modulating NLRP3 expression. Thus, TUDCA may be a promising drug for DPN therapy.
Revisiting the Importance of Sulfur Electrode‐Current‐Collector Interface in Lithium‐Sulfur Batteries
Authors: Reis Albin Conde , Yari Saeed , D'Haen Jan , Hardy An , Reddy Naveen , Safari Mohammadhosein
Published: September 2023

This work demonstrates that, in lithium‐sulfur (Li‐S) batteries, the presence of the carbon/binder domain is more crucial at the vicinity of the current collector rather than in the bulk of the electrode. The electrode composition at the current collector interface is showcased to significantly impact the energy density, rate performance, reproducibility, and mechanical attributes of the Li‐S cells made thereof. The coating of a micrometric interlayer composed of carbon/binder at the current collector‐electrode interface is shown to be a promising avenue for the formulation of the sulfur electrodes with a low dead mass and volume while preserving a low polarization and high sulfur utilization. The short‐term spatial redistribution of the solid (dis)charge end‐products is tracked revealing the preferential precipitation of the S and Li2S at large cavities and near the current collector, respectively. The non‐uniform transformations inside the sulfur electrode is further corroborated by detecting and analyzing the precipitation waves inside a pressure electrochemical cell.
Consumer financial planning in the post‐Covid‐19 era: The role of emotional and economic vulnerability
Authors: Allanjawi Khulood M. , Yazdanparast Atefeh , Alhenawi Yasser
Published: September 2023

The present research examines the relationship between emotional vulnerability, economic vulnerability, and intentions to improve financial planning for American households in the post‐Covid‐19 era. Using a survey of 504 household financial decision markers, we show that the effects of psychological fears and concerns experienced during the pandemic (i.e., emotional vulnerability) on post‐pandemic household financial planning intentions are mediated by their perceived economic vulnerability. Specifically, for those who experience higher levels of emotional vulnerability, economic vulnerabilities are perceived to be harsher, further motivating them to raise their financial preparedness. Moreover, we identify an individual factor, personality trait of conscientiousness, as a boundary condition affecting this relationship. Specifically, individuals who are more conscientious tend to be more willing to learn from harsh pandemic experiences and are more willing to adapt in the long run.
Pachymic acid (PA) inhibits ferroptosis of cardiomyocytes via activation of the AMPK in mice with ischemia/reperfusion‐induced myocardial injury
Authors: Liu Dongmin , Ding Jiru , Li Zhenzhen , Lu Youquan
Published: September 2023

Pachymic acid (PA) is a lanostane‐type triterpenoid with various pharmacological effects. However, little is known about the effect of PA on myocardial infarction (MI) induced by ischemia/reperfusion (I/R). In this study, we aimed to investigate the protective effect of PA and its underlying mechanism. A cellular MI model was established by oxygen‐glucose deprivation and reperfusion (OGD/R) treatment in HL‐1 cardiomyocytes, and we found that OGD/R treatment decreased cell viability and glutathione peroxide (GSH‐Px) activity, increased Fe2+ concentration and lactate dehydrogenase (LDH) activity, promoted malondialdehyde (MDA) and reactive oxygen species (ROS) production, and inhibited the expression of ferroptosis marker proteins SLC7A11 and GPX4 in a time‐dependent manner. OGD/R‐induced HL‐1 cells were pretreated with different concentrations of PA (0, 20, 40, 60 μg/mL) for 24 h, and toxicological experiments showed that 150 μg/mL PA decreased cell viability, while low concentrations of PA had no toxic effect on cells. 20 μg/mL PA reversed the inhibitory effect of OGD/R on cell viability, reduced MDA and ROS production, and Fe2+ accumulation, increased GSH‐Px activity and the expression of SLC7A11 and GPX4, and decreased LDH activity, especially at 60 μg/mL PA. Meanwhile, PA promoted the phosphorylation of IRS‐1, AKT, and AMPK proteins in a dose‐dependent manner. AICAR, an AMPK activator, inhibited ferroptosis, while STO‐609, an AMPK inhibitor, largely abolished the effect of PA on OGD/R‐induced ferroptosis of HL‐1 cells. In addition, PA inhibited ferroptosis and myocardial I/R injury in wild‐type mice and AMPK knockout (AMPK−/−) mice. Collectively, PA inhibited ferroptosis of cardiomyocytes through activating of the AMPK pathway, thereby alleviating myocardial I/R injury in mice.
Use of baclofen and propranolol for treatment of neurogenic fever in a patient with pontine hemorrhage: A case report
Authors: Poudel Saroj , Chalise Rupak , Bist Manoj , Regmi Ashim , Ghimire Anup , Khanal Kishor
Published: September 2023

Key Clinical Message

Neurogenic fever (NF) is a potentially life‐threatening complication commonly seen in patients with pontine hemorrhage. This case report highlights the successful use of oral baclofen and propranolol as an effective treatment strategy to manage NF.

Neurogenic fever (NF) is a common complication following pontine hemorrhage and poses significant challenges for clinicians in terms of diagnosis, management, and patient outcomes. This study delves into the efficacy of treatment methods involving baclofen and propranolol for neurogenic fever in patients with pontine hemorrhage. The results demonstrated a significant reduction in the duration and intensity of fever. Moreover, the treatment modality was well‐tolerated and devoid of any adverse effects. These findings suggest that the use of oral baclofen and propranolol may be a promising therapeutic option for managing neurogenic fever in patients with pontine hemorrhage.
Controlling the Assembly of PdII/Bianthryl‐Based Monomeric and Dimeric Interlocked Cages by Steric Effects
Authors: Watanabe Sota , Yamashina Masahiro , Tsurumaki Eiji , Toyota Shinji
Published: September 2023

In the energy landscape of coordination‐driven self‐assembly processes, the isolation of kinetically formed supramolecular cages has long been identified as a challenging task. This study reports a reliable strategy for the selective isolation of kinetically or thermodynamically preferred stable coordination cages, whose formation depends on the degree of steric protection offered by the exterior side chains. The combination of PdII ions with arc‐shaped 2,2′‐bianthryl‐based ligands that contain different numbers of methoxyethoxy side chains led to the quantitative formation of both kinetically favorable monomeric M2L4 cages and thermodynamically favorable dimeric (M2L4)2 interlocked cages. These assemblies were structurally fully characterized via NMR spectroscopy, mass spectrometry, and single‐crystal X‐ray diffraction analysis. Although the monomeric cages with fewer exterior side chains can reassemble into interlocked cages, the cages with more exterior substituents remain monomeric cages under similar conditions. A computational study revealed that this different behavior is mainly governed by the destabilization of the interlocking assemblies due to the steric repulsion among the side chains on the overcrowded exterior. Furthermore, the kinetically stabilized monomeric M2L4 cages exhibit permanent host abilities toward sulfonate guests, while the cages with lower steric protection undergo dimerization accompanied by guest release.
Binding Properties of Small Electrophilic Anions [B6X5]− and [B10X9]− (X=Cl, Br, I): Activation of Small Molecules Based on π‐Backbonding
Authors: Kawa Sebastian , Knorke Harald , Jin Jiaye , Rohdenburg Markus , Asmis Knut R. , Tonner‐Zech Ralf , Bernhardt Eduard , Jenne Carsten , Finze Maik , Warneke Jonas
Published: September 2023

Superelectrophilic anions constitute a special class of molecular anions that show strong binding of weak nucleophiles despite their negative charge. In this study, the binding characteristics of smaller gaseous electrophilic anions of the types [B6X5]− and [B10X9]− (with X=Cl, Br, I) were computationally and experimentally investigated and compared to those of the larger analogues [B12X11]−. The positive charge of vacant boron increases from [B6X5]− via [B10X9]− to [B12X11]−, as evidenced by increasing attachment enthalpies towards typical σ‐donor molecules (noble gases, H2O). However, this behavior is reversed for σ‐donor–π‐acceptor molecules. [B6Cl5]− binds most strongly to N2 and CO, even more strongly than to H2O. Energy decomposition analysis confirms that the orbital interaction is responsible for this opposite trend. The extended transition state natural orbitals for chemical valence method shows that the π‐backdonation order is [B6X5]−>[B10X9]−>[B12X11]−. This predicted order explains the experimentally observed red shifts of the CO and N2 stretching fundamentals compared to those of the unbound molecules, as measured by infrared photodissociation spectroscopy. The strongest red shift is observed for [B6Cl5N2]−: 222 cm−1. Therefore, strong activation of unreactive σ‐donor–π‐acceptor molecules (commonly observed for cationic transition metal complexes) is achieved with metal‐free molecular anions.
Virus‐Bionic Mesoporous Silica Nanoplatform for Malignant Tumor Inhibition via Effective Cellular Uptake and Precise Drug Delivery
Authors: Yang Xiyang , Xie Yilin , Liao Xiaoli , Zheng Tingting
Published: September 2023

Over the past few decades, sophisticated nanomaterials have been used as carries for the targeted delivery of therapeutics to solid tumors. However, the low efficiency of intracellular internalization of nanocarriers in current use restricts their biomedical application. In this work, we demonstrate that novel virus‐bionic mesoporous‐silica‐based nanocarriers can be successfully prepared for programmed precise drug delivery. These unique viral mimic nanovesicles not only present virus bionic counterparts and nanostructures, but also have infectious virus‐like properties toward tumor cells and tumor tissues. Encouragingly, their large surface area (322.1 m2/g) endows them with high loading capacity for therapeutic agents, especially, they have more effective gene transfection properties than the commercially available LipoGeneTM transfection reagent. Thanks to their virus‐inspired morphology, they exhibit outstanding cellular uptake efficiency with living tumor cells and the ability to invade cells in large quantities with incubation times as short as 5 min, which is much faster than traditional mesoporous silica nanoparticles (mSN) with smooth appearance. Importantly, after doxorubicin (DOX) loading and surface modification of tumor recognition motifs, RGD (Arg‐Gly‐Asp, vMN@DOX‐RGD), the bionic drug‐loaded viral mimics elicit potent tumor cell elimination both in vitro and in vivo, greatly exceeding the mSN‐based group. Our work paves the way toward virus bionic nanocarrier design for malignant tumor suppression in the clinic.
Trauma and sporadic desmoid tumor development: An approach toward real incidence and aspects of causality
Authors: Hohenberger Peter , Menge Franka , Hohenberger Ralph , Kasper Bernd , Marx Alexander , Haller Florian , Baumgarten Christina , Wardelmann Eva , Jakob Jens
Published: September 2023

Objectives

The development of desmoid tumors (DT) is associated with trauma, which is an aspect with medicolegal relevance. The objective of this study was to analyze the proportion and type of trauma (surgical, blunt/fracture, implants), its lag time, and mutations of the CTNNB1 gene in patients with sporadic DT.

Methods

We analyzed a prospectively kept database of 381 females and 171 males, median age at disease onset 37.7 years (females) and 39.3 years (males) with a histologically confirmed DT. Patients with germline mutation of the APC gene were excluded. Details of the history particularly of traumatic injuries to the site of DT were provided by 501 patients.

Results

In 164 patients (32.7%), a trauma anteceding DT could be verified with a median lag time of 22.9 months (SD, 7.7 months; range, 9‐44 months). A prior surgical procedure was relevant in 98 patients, a blunt trauma in 35 patients, a punctuated trauma (injections, trocar) in 18 patients, and site of an implant in 10 patients. In 220 patients, no trauma was reported (43.9%), and 58 females (11.6%) had a postpregnancy DT in the rectus abdominis muscle. In 42 patients (8.4%), data were inconclusive. The distribution of mutations in the CTNNB1 gene (codon 41 vs. 45) was similar in patients with and without a history of trauma before DT development.

Conclusions

A significant subgroup of patients suffers from a trauma‐associated DT, predominantly at a prior surgical site including implants to breast or groin, accounting for 77.9% of the cases, whereas blunt trauma was responsible in 22.1%. We found no data to support that trauma‐associated DT have different molecular features in the CTNNB1 gene.
Asymmetric Reduction of Cyclic Imines by Imine Reductase Enzymes in Non‐Conventional Solvents
Authors: Arnodo Davide , De Nardi Federica , Parisotto Stefano , De Nardo Eugenio , Cananà Stefania , Salvatico Federica , De Marchi Elisa , Scarpi Dina , Blangetti Marco , Occhiato Ernesto G. , Prandi Cristina
Published: September 2023

The first enantioselective reduction of 2‐substituted cyclic imines to the corresponding amines (pyrrolidines, piperidines, and azepines) by imine reductases (IREDs) in non‐conventional solvents is reported. The best results were obtained in a glycerol/phosphate buffer 1 : 1 mixture, in which heterocyclic amines were produced with full conversions (>99 %), moderate to good yields (22–84 %) and excellent S‐enantioselectivities (up to >99 % ee). Remarkably, the process can be performed at a 100 mM substrate loading, which, for the model compound, means a concentration of 14.5 g L−1. A fed‐batch protocol was also developed for a convenient scale‐up transformation, and one millimole of substrate 1 a was readily converted into 120 mg of enantiopure amine (S)‐2 a with a remarkable 80 % overall yield. This aspect strongly contributes to making the process potentially attractive for large‐scale applications in terms of economic and environmental sustainability for a good number of substrates used to produce enantiopure cyclic amines of high pharmaceutical interest.
Cost‐optimized Internet of Things application deployment in edge computing environment
Authors: Tang Bing , Zhang Xiaoyuan , Yang Qing , Qi Xin , Alqahtani Fayez , Tolba Amr
Published: September 2023

With the increasing popularity of cloud native and DevOps, container technology has become widely used in combination with microservices. However, deploying container‐based microservices in distributed edge‐cloud infrastructure requires complex selection strategies to ensure high‐quality service for users. Existing container orchestration tools lack flexibility in selecting the best deployment location based on user cost budgets and are insufficient in providing personalized deployment solutions. This paper proposes a genetic algorithm‐based Internet of Things (IoT) application deployment and selection strategy for personalized cost budgets. The application deployment problem is defined as an optimization problem that minimizes user service latency under cost constraints, which is an NP‐hard problem. The genetic algorithm is introduced to solve this problem effectively and improve deployment efficiency. Comparative results show that the proposed algorithm outperforms four baseline algorithms, including time‐greedy, cost‐greedy, random, and PSO, using real datasets and some synthetic datasets. The proposed algorithm provides personalized deployment solutions for edge‐cloud infrastructure.
Influence of multiple human chorionic gonadotropin administrations on serum and urinary steroid Athlete Biological Passport profiles in males
Authors: Goodrum Jenna M. , Moore Chad , Crouch Andre K. , Eichner Daniel , Miller Geoffrey D.
Published: September 2023

The Athlete Biological Passport (ABP) is a longitudinal tool used in anti‐doping to monitor biological parameters known to change with performance‐enhancing drug use. The ABP consists of multiple modules, including two aimed at detecting the use of endogenous anabolic androgenic steroids: the urinary and serum steroid modules. Human chorionic gonadotropin (hCG) is a protein hormone potentially abused by male athletes to increase the production of endogenous testosterone. To date, no studies have investigated the impact of extended hCG administration on the urinary and serum steroid modules of the ABP. The goal of this study was to identify the impact of multiple hCG administrations on the parameters tracked as part of the urinary and serum steroid modules of the ABP. Ten recreationally active, healthy male individuals self‐administered seven 250 μg hCG injections over 3 weeks. Serum and urine samples were collected before, during, and 2 weeks following the final injection. All ABP parameters were quantified in the respective matrix, and steroid profiles were created with Anti‐Doping Administration and Management System adaptive model upper and lower limits for both matrices. In both serum and urine profiles, testosterone increased; however, the testosterone/epitestosterone ratio in urine and the testosterone/androstenedione ratio in serum showed minimal changes. Additionally, serum luteinizing hormone (LH) was quantified using an immunoassay, and a serum testosterone/LH ratio was generated. Serum LH values decreased during administration causing large increases in the serum T/LH ratio, indicating this ratio may be a more sensitive parameter for detecting hCG abuse than urinary testosterone/epitestosterone or serum testosterone/androstenedione.
One‐Pot Synthesis of Fused Tetrahydroquinoline‐Iminosugar Derivatives
Authors: Wu Jilai , Xie Song , Xu Xin , Zhou Ziyi , Zhou Likai , Wei Chao , Li Xiaoliu , Wu Chen , Chen Hua
Published: September 2023

An efficient and simple one‐pot synthesis of structurally diverse novel tetrahydroquinoline‐fused iminosugars was developed through the aza‐Diels‐Alder mechanism. The adaptability of this method has been demonstrated by a variety of imines and d/l‐ribose tosylates, and both, electron‐donating and ‐withdrawing substituted imines proceed well. In addition, this reaction is characterized by simple operation, good yield, and high atom economy. Some synthetic iminosugars showed moderate anti proliferation of HCT116 tumor cells.
Photovoltaic Thermal Technology Collectors, Systems, and Applications
Authors: Kramer Korbinian S. , Mehnert Stefan , Munz Gunther , Helmling Sebastian , Lämmle Manuel
Published: September 2023

Photovoltaic thermal (PVT) technology has been drawing attention recently. Electrification of the heating sector with heat pumps run by carbon‐free electricity sources like photovoltaics is setting the ground for the interest. This article gives insight into PVT technologies and collector designs according to application and operating temperatures. For most conventional designs, examples like prototypes from Research & Development projects are presented. In addition, commercial products are listed along these categories, and the influence on the gross thermal and electrical yield is depicted based on Solar Keymark certification data. The process of certification is presented in a comprehensive way, showing current limitations, giving an outlook on the most recent approach for enhanced procedures and specifications. Finally, different system layouts are presented, and examples from installations combined with a heat pump are given with their specific performances. Real performance data of several PVT installations are compared to conventional heat pump systems. The identified seasonal performance factors are in a range from 3.4 to 4.2 and in between air source and ground source heat pumps. Continuous monitoring and derived data are enablers to discover the decisive influence of the system layout and dimensioning on performance indicators like, for example, operating temperatures over the year.
Dravet syndrome: A systematic literature review of the illness burden
Authors: Strzelczyk Adam , Lagae Lieven , Wilmshurst Jo M , Brunklaus Andreas , Striano Pasquale , Rosenow Felix , Schubert‐Bast Susanne
Published: September 2023

We performed a systematic literature review and narrative synthesis according to a pre‐registered protocol (Prospero: CRD42022376561) to identify the evidence associated with the burden of illness in Dravet syndrome (DS), a developmental and epileptic encephalopathy characterized by drug‐resistant epilepsy with neurocognitive and neurobehavioral impairment. We searched MEDLINE, Embase, and APA PsychInfo, Cochrane's database of systematic reviews, and Epistemonikos from inception to June 2022. Non‐interventional studies reporting on epidemiology (incidence, prevalence, and mortality), patient and caregiver health‐related quality of life (HRQoL), direct and indirect costs and healthcare resource utilization were eligible. Two reviewers independently carried out the screening. Pre‐specified data were extracted and a narrative synthesis was conducted. Overall, 49 studies met the inclusion criteria. The incidence varied from 1:15 400–1:40 900, and the prevalence varied from 1.5 per 100 000 to 6.5 per 100 000. Mortality was reported in 3.7%–20.8% of DS patients, most commonly due to sudden unexpected death in epilepsy and status epilepticus. Patient HRQoL, assessed by caregivers, was lower than in non‐DS epilepsy patients; mean scores (0 [worst] to 100/1 [best]) were 62.1 for the Kiddy KINDL/Kid‐KINDL, 46.5–54.7 for the PedsQL and 0.42 for the EQ‐5D‐5L. Caregivers, especially mothers, were severely affected, with impacts on their time, energy, sleep, career, and finances, while siblings were also affected. Symptoms of depression were reported in 47%–70% of caregivers. Mean total direct costs were high across all studies, ranging from $11 048 to $77 914 per patient per year (PPPY), with inpatient admissions being a key cost driver across most studies. Mean costs related to lost productivity were only reported in three publications, ranging from approximately $19 000 to $20 000 PPPY ($17 596 for mothers vs $1564 for fathers). High seizure burden was associated with higher resource utilization, costs and poorer HRQoL. The burden of DS on patients, caregivers, the healthcare system, and society is profound, reflecting the severe nature of the syndrome. Future studies will be able to assess the impact that newly approved therapies have on reducing the burden of DS.
Health and illness beliefs regarding pain and pain management of New Zealand resident Sāmoan community leaders: A qualitative interpretive study based on Pasifika paradigms
Authors: Upsdell Angela , Fia'ali'i Jessee , Lewis Gwyn N. , Terry Gareth
Published: September 2023

Issue Addressed

Ethnic disparities in chronic pain exist in Aotearoa New Zealand, including a greater impact of pain, less access to chronic pain services and less benefit from treatment for Pasifika people. This study investigated Sāmoan health perceptions and beliefs in relation to pain and how it is managed.

Methods

An interpretive descriptive study was undertaken involving interviews with nine Sāmoan key informants from Aotearoa New Zealand. Interviews explored their beliefs in relation to interpretations of pain and experiences of and preferences for pain management. Interviews were recorded and transcribed. Data were analysed using thematic analysis.

Results

Four main themes were constructed from the data. Pain is interpreted holistically described the attribution of pain to many causes, without limitation to physiological explanations. Stoicism is a character virtue described the predominant belief that pain should be endured without display or complaint. Strength in connectivity described the inherent pain coping strategies that are present within Sāmoan communities. To improve healthcare is to nurture vā described the disconnect Sāmoan people feel from healthcare services and the need to foster relationships to improve health delivery.

Conclusions

Sāmoan people have beliefs and perceptions about pain and its management that extend beyond traditional Western interpretations. While pain is often endured using traditional strengths within the ‘āīga (family) and community, the Sāmoan community faces challenges in receiving healthcare from mainstream pain services.

So What?

Clinicians need to foster stronger relationships with Sāmoan individuals and their ‘āīga and appreciate the wider psychosocial context of pain, including spirituality.
Analyze the clinical effect of YAG laser combined with sodium hypochlorite in root canal treatment of pulpitis
Authors: Lin Qiaolin , Li Zhixin , Liu Mingming
Published: September 2023

Objective

To compare and analyze the clinical therapeutic effects of sodium hypochlorite combined with Nd: YAG laser and sodium hypochlorite alone for root canal disinfection in patients with pulpitis.

Methods

Patients with pulpitis were divided into control group and observation group according to random number table method. Both groups received root canal treatment, while the control group received root canal irrigation with 1% sodium hypochlorite. The observation group was irrigated with 1% sodium hypochlorite combined with Nd: YAG laser. Periodontal index, inflammatory index, life quality score and bacterial infection clearance rate of the two groups were compared before and 3 months after treatment.

Results

The total effective rate of the observation group was 95.35%, which was higher than that of the control group 79.07% (p < .05). After 3 months of treatment, the periodontal index and inflammation level of both groups decreased, and the observation group was lower than that in the control group (p < .05). The life quality score and infection clearance rate of observation group were significantly higher than control group (p < .05).

Conclusion

Compared with root canal irrigation with 1% sodium hypochlorite alone, sodium hypochlorite combined with Nd: YAG laser for root canal disinfection can significantly improve the therapeutic effect, relieve inflammatory reaction, and decrease bacterial infection.
Interaction among inflammasome, PANoptosise, and innate immune cells in infection of influenza virus: Updated review
Authors: Wei Li , Wang Xufang , Zhou Huifei
Published: September 2023

Background

Influenza virus (IV) is a leading cause of respiratory tract infections, eliciting responses from key innate immune cells such as Macrophages (MQs), Neutrophils, and Dendritic Cells (DCs). These cells employ diverse mechanisms to combat IV, with Inflammasomes playing a pivotal role in viral infection control. Cellular death mechanisms, including Pyroptosis, Apoptosis, and Necroptosis (collectively called PANoptosis), significantly contribute to the innate immune response.

Methods

In this updated review, we delve into the intricate relationship between PANoptosis and Inflammasomes within innate immune cells (MQs, Neutrophils, and DCs) during IV infections. We explore the strategies employed by IV to evade these immune defenses and the consequences of unchecked PANoptosis and inflammasome activation, including the potential development of severe complications such as cytokine storms and tissue damage.

Results

Our analysis underscores the interplay between PANoptosis and Inflammasomes as a critical aspect of the innate immune response against IV. We provide insights into IV's various mechanisms to subvert these immune pathways and highlight the importance of understanding these interactions to develop effective antiviral medications.

Conclusion

A comprehensive understanding of the dynamic interactions between PANoptosis, Inflammasomes, and IV is essential for advancing our knowledge of innate immune responses to viral infections. This knowledge will be invaluable in developing targeted antiviral therapies to combat IV and mitigate potential complications, including cytokine storms and tissue damage.