bluuebunny/crossref_metadata_2025 huggingface dataset:
Job morale of physicians and dentists in Kazakhstan: a qualitative study
Authors: Sabitova Alina , Hickling Lauren M. , Toleubayev Medet , Jovanović Nikolina , Priebe Stefan
Published: December 2022

Background

Job morale is thought to be particularly low in Kazakhstan, adversely affecting job motivation, job satisfaction and burnout rates. Previous research suggests that high job morale has a better effect on patient outcomes and care quality. We, therefore, conducted a qualitative study to explore experiences underpinning positive and negative job morale, and to generate potential strategies for improving job morale of physicians and dentists working in public healthcare settings in Kazakhstan prior to the COVID-19 pandemic.

Methods

Three focus groups containing 23 participants and 30 individual interviews were conducted, evidencing respondents' explanations of what affects job morale, and possible strategies to improve it. Data was synthesised using a thematic analysis.

Results

The themes about what influences job morale were: being unfairly rewarded for work; feeling vulnerable and undervalued; poor working styles and practices; and high internal value-based motivation. Various strategies were identified by participants to improve job morale, and these included: ensuring adequate and equitable financial income; improving the current malpractice system; eliminating poor working styles and practices; and creating a shared responsibility for health.

Conclusions

The current study has found that despite prevailing threats, job morale amongst physicians and dentists working in public healthcare settings in Astana have been prevented from becoming negative by their strong sense of calling to medicine and the satisfaction of helping patients recover. Emphasising this rather traditional understanding of the role of physicians and dentists may be a way to improve job morale throughout training and practice.
Involvement of miRNA-34a regulated Krüppel-like factor 4 expression in hyperoxia-induced senescence in lung epithelial cells
Authors: Maeda Hajime , Yao Hongwei , Go Hayato , Huntington Kelsey E. , De Paepe Monique E. , Dennery Phyllis A.
Published: December 2022

Background

Premature infants, subjected to supplemental oxygen and mechanical ventilation, may develop bronchopulmonary dysplasia, a chronic lung disease characterized by alveolar dysplasia and impaired vascularization. We and others have shown that hyperoxia causes senescence in cultured lung epithelial cells and fibroblasts. Although miR-34a modulates senescence, it is unclear whether it contributes to hyperoxia-induced senescence. We hypothesized that hyperoxia increases miR-34a levels, leading to cellular senescence.

Methods

We exposed mouse lung epithelial (MLE-12) cells and primary human small airway epithelial cells to hyperoxia (95% O2/5% CO2) or air (21% O2/5% CO2) for 24 h. Newborn mice (< 12 h old) were exposed to hyperoxia (> 95% O2) for 3 days and allowed to recover in room air until postnatal day 7. Lung samples from premature human infants requiring mechanical ventilation and control subjects who were not mechanically ventilated were employed.

Results

Hyperoxia caused senescence as indicated by loss of nuclear lamin B1, increased p21 gene expression, and senescence-associated secretory phenotype factors. Expression of miR-34a-5p was increased in epithelial cells and newborn mice exposed to hyperoxia, and in premature infants requiring mechanical ventilation. Transfection with a miR-34a-5p inhibitor reduced hyperoxia-induced senescence in MLE-12 cells. Additionally, hyperoxia increased protein levels of the oncogene and tumor-suppressor Krüppel-like factor 4 (KLF4), which were inhibited by a miR-34a-5p inhibitor. Furthermore, KLF4 knockdown by siRNA transfection reduced hyperoxia-induced senescence.

Conclusion

Hyperoxia increases miR-34a-5p, leading to senescence in lung epithelial cells. This is dictated in part by upregulation of KLF4 signaling. Therefore, inhibiting hyperoxia-induced senescence via miR-34a-5p or KLF4 suppression may provide a novel therapeutic strategy to mitigate the detrimental consequences of hyperoxia in the neonatal lung.
d-Limonene inhibits the occurrence and progression of LUAD through suppressing lipid droplet accumulation induced by PM2.5 exposure in vivo and in vitro
Authors: Zhu Tengteng , Li Yangyang , Feng Tienan , Yang Yuqing , Zhang Kai , Gao Jing , Quan Xiaowei , Qian Ying , Yu Herbert , Qian Biyun
Published: December 2022

Background

PM2.5 exposure is associated with lung adenocarcinoma (LUAD), but the mechanism is unclear. The lack of understanding impedes our effort on prevention. This study examined a possible mechanism of lung cancer caused by PM2.5 exposure, and aimed to find a potential intervention for people living in PM2.5 polluted regions.

Methods

Electron microscopy and oil-red staining were conducted to examine the lipid droplet accumulation. Masson’s trichrome staining, colony forming, scratch assay and transwell experiment were conducted to evaluate the effect of PM2.5 exposure and d-limonene intervention on the occurrence and progression of LUAD. Potential intervention targets were found by RNA-Seq and verified by luciferase reporter assay. MiR-195 KO mice constructed with CRISPR/Cas9 technology were used to investigate the pivotal role of d-limonene-miR-195-SREBP1/FASN axis. Cohort analysis of lung cancer patients, human LUAD tissues staining and human intervention trial were also conducted to validate the results of cell and animal experiments.

Results

Our results showed that PM2.5 exposure induced accumulation of lipid droplets in LUAD cells which accompanied by increased malignant cellular behaviors. PM2.5 exposure led to cleaved N-SREBP1 translocation into nucleus, which activated the de novo lipogenesis pathway. Same changes were also observed in normal lung epithelial cells and normal lung tissue, and mice developed pulmonary fibrosis after long-term exposure to PM2.5. Furthermore, in a cohort of 11,712 lung cancer patients, significant lipid metabolism disorders were observed in higher PM2.5 polluted areas. In view of that, d-limonene was found to inhibit the changes in lipid metabolism through upregulating the expression of miR-195, which inhibited the expression of lipogenic genes (SREBF1/FASN/ACACA) specifically. And a small human intervention trial showed that serum miR-195 was upregulated after oral intake of d-limonene.

Conclusion

Our findings reveal a new mechanism of pulmonary fibrosis and LUAD that is related to PM2.5 exposure-induced lipid droplet accumulation. We also demonstrate that d-limonene-miR-195-SREBP1/FASN axis is a potential preventive intervention for mediating the progression and development of LUAD induced by PM2.5 exposure.

Trial registration Chinese Clinical Trial Registry, ChiCTR2000030200. Registered 25 February 2020, http://www.chictr.org.cn/showproj.aspx?proj=48013

Graphical Abstract
New variants of alpha-1-antitrypsin: structural simulations and clinical expression
Authors: Gonzalez Angel , Belmonte Irene , Nuñez Alexa , Farago Georgina , Barrecheguren Miriam , Pons Mònica , Orriols Gerard , Gabriel-Medina Pablo , Rodríguez-Frías Francisco , Miravitlles Marc , Esquinas Cristina
Published: December 2022

Background

Alpha-1 antitrypsin deficiency (AATD) is characterized by reduced serum levels of the AAT protein and predisposes to liver and lung disease. The characterization at structural level of novel pathogenic SERPINA1 mutants coding for circulating AAT could provide novel insights into the mechanisms of AAT misfolding. The present study aimed to provide a practical framework for the identification and analysis of new AAT mutations, combining structural simulations and clinical data.

Methods

We analysed a total of five mutations (four not previously described) in a total of six subjects presenting moderate to severe AATD: Gly95Alafs*18, Val210Glu, Asn247Ser, Pi*S + Asp341His and Pi*S + Leu383Phe + Lys394Ile. Clinical data, genotyping and phenotyping assays, structural mapping, and conformational characterization through molecular dynamic (MD) simulations were developed and combined.

Results

Newly discovered AAT missense variants were localized both on the interaction surface and the hydrophobic core of the protein. Distribution of mutations across the structure revealed Val210Glu at the solvent exposed s4C strand and close to the “Gate” region. Asn247Ser was located on the accessible surface, which is important for glycan attachment. On the other hand, Asp341His, Leu383Phe were mapped close to the “breach” and “shutter” regions. MD analysis revealed the reshaping of local interactions around the investigated substitutions that have varying effects on AAT conformational flexibility, hydrophobic packing, and electronic surface properties. The most severe structural changes were observed in the double- and triple-mutant (Pi*S + Asp341His and Pi*S + Leu383Phe + Lys394Ile) molecular models. The two carriers presented impaired lung function.

Conclusions

The results characterize five variants, four of them previously unknown, of the SERPINA1 gene, which define new alleles contributing to the deficiency of AAT. Rare variants might be more frequent than expected, and therefore, in discordant cases, standardized screening of the S and Z alleles needs complementation with gene sequencing and structural approaches. The utility of computational modelling for providing supporting evidence of the pathogenicity of rare single nucleotide variations is discussed.
Highly efficient fermentation of 5-keto-d-fructose with Gluconobacter oxydans at different scales
Authors: Battling Svenja , Engel Tobias , Herweg Elena , Niehoff Paul-Joachim , Pesch Matthias , Scholand Theresa , Schöpping Marie , Sonntag Nina , Büchs Jochen
Published: December 2022

Background

The global market for sweeteners is increasing, and the food industry is constantly looking for new low-caloric sweeteners. The natural sweetener 5-keto-d-fructose is one such candidate. 5-Keto-d-fructose has a similar sweet taste quality as fructose. Developing a highly efficient 5-keto-d-fructose production process is key to being competitive with established sweeteners. Hence, the 5-keto-d-fructose production process was optimised regarding titre, yield, and productivity.

Results

For production of 5-keto-d-fructose with G. oxydans 621H ΔhsdR pBBR1-p264-fdhSCL-ST an extended-batch fermentation was conducted. During fructose feeding, a decreasing respiratory activity occurred, despite sufficient carbon supply. Oxygen and second substrate limitation could be excluded as reasons for the decreasing respiration. It was demonstrated that a short period of oxygen limitation has no significant influence on 5-keto-d-fructose production, showing the robustness of this process. Increasing the medium concentration increased initial biomass formation. Applying a fructose feeding solution with a concentration of approx. 1200 g/L, a titre of 545 g/L 5-keto-d-fructose was reached. The yield was with 0.98 g5-keto-d-fructose/gfructose close to the theoretical maximum. A 1200 g/L fructose solution has a viscosity of 450 mPa∙s at a temperature of 55 °C. Hence, the solution itself and the whole peripheral feeding system need to be heated, to apply such a highly concentrated feeding solution. Thermal treatment of highly concentrated fructose solutions led to the formation of 5-hydroxymethylfurfural, which inhibited the 5-keto-d-fructose production. Therefore, fructose solutions were only heated to about 100 °C for approx. 10 min. An alternative feeding strategy was investigated using solid fructose cubes, reaching the highest productivities above 10 g5-keto-d-fructose/L/h during feeding. Moreover, the scale-up of the 5-keto-d-fructose production to a 150 L pressurised fermenter was successfully demonstrated using liquid fructose solutions (745 g/L).

Conclusion

We optimised the 5-keto-d-fructose production process and successfully increased titre, yield and productivity. By using solid fructose, we presented a second feeding strategy, which can be of great interest for further scale-up experiments. A first scale-up of this process was performed, showing the possibility for an industrial production of 5-keto-d-fructose.
Extracellular vesicles from IFN-γ-primed mesenchymal stem cells repress atopic dermatitis in mice
Authors: Kim Jimin , Lee Seul Ki , Jung Minyoung , Jeong Seon-Yeong , You Haedeun , Won Ji-Yeon , Han Sang-Deok , Cho Hye Jin , Park Somi , Park Joonghoon , Kim Tae Min , Kim Soo
Published: December 2022

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune dysregulation, pruritus, and abnormal epidermal barrier function. Compared with conventional mesenchymal stem cell (MSC), induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) is recognized as a unique source for producing extracellular vesicles (EVs) because it can be obtained in a scalable manner with an enhanced homogeneity. Stimulation of iMSCs with inflammatory cytokines can improve the immune-regulatory, anti-inflammatory, and tissue-repairing potential of iMSC-derived EVs.

Results

Proteome analysis showed that IFN-γ-iMSC-EVs are enriched with protein sets that are involved in regulating interferon responses and inflammatory pathways. In AD mice, expression of interleukin receptors for Th2 cytokines (IL-4Rα/13Rα1/31Rα) and activation of their corresponding intracellular signaling molecules was reduced. IFN-γ-iMSC-EVs decreased itching, which was supported by reduced inflammatory cell infiltration and mast cells in AD mouse skin; reduced IgE receptor expression and thymic stromal lymphopoietin and NF-kB activation; and recovered impaired skin barrier, as evidenced by upregulation of key genes of epidermal differentiation and lipid synthesis.

Conclusions

IFN-γ-iMSC-EVs inhibit Th2-induced immune responses, suppress inflammation, and facilitate skin barrier restoration, contributing to AD improvement.
Repellent active ingredients encapsulated in polymeric nanoparticles: potential alternative formulations to control arboviruses
Authors: Abrantes Daniele Carvalho , Rogerio Carolina Barbara , Campos Estefânia Vangelie Ramos , Germano-Costa Tais , Vigato Aryane Alves , Machado Ian Pompermeyer , Sepulveda Anderson Ferreira , Lima Renata , de Araujo Daniele Ribeiro , Fraceto Leonardo Fernandes
Published: December 2022

Dengue, yellow fever, Chinkungunya, Zika virus, and West Nile fever have infected millions and killed a considerable number of humans since their emergence. These arboviruses are transmitted by mosquito bites and topical chemical repellents are the most commonly used method to protect against vector arthropod species. This study aimed to develop a new generation of repellent formulations to promote improved arboviruses transmission control. A repellent system based on polycaprolactone (PCL)-polymeric nanoparticles was developed for the dual encapsulation of IR3535 and geraniol and further incorporation into a thermosensitive hydrogel. The physicochemical and morphological parameters of the prepared formulations were evaluated by dynamic light scattering (DLS), nano tracking analysis (NTA), atomic force microscopy (AFM). In vitro release mechanisms and permeation performance were evaluated before and after nanoparticles incorporation into the hydrogels. FTIR analysis was performed to evaluate the effect of formulation epidermal contact. Potential cytotoxicity was evaluated using the MTT reduction test and disc diffusion methods. The nanoparticle formulations were stable over 120 days with encapsulation efficiency (EE) of 60% and 99% for IR3535 and geraniol, respectively. AFM analysis revealed a spherical nanoparticle morphology. After 24 h, 7 ± 0.1% and 83 ± 2% of the GRL and IR3535, respectively, were released while the same formulation incorporated in poloxamer 407 hydrogel released 11 ± 0.9% and 29 ± 3% of the loaded GRL and IR3535, respectively. GRL permeation from PCL nanoparticles and PCL nanoparticles in the hydrogel showed similar profiles, while IR3535 permeation was modulated by formulation compositions. Differences in IR3535 permeated amounts were higher for PCL nanoparticles in the hydrogels (36.9 ± 1.1 mg/cm2) compared to the IR3535-PCL nanoparticles (29.2 ± 1.5 mg/cm2). However, both active permeation concentrations were low at 24 h, indicating that the formulations (PCL nanoparticles and PCL in hydrogel) controlled the bioactive percutaneous absorption. Minor changes in the stratum corneum (SC) caused by interaction with the formulations may not represent a consumer safety risk. The cytotoxicity results presented herein indicate the carrier systems based on poly-epsilon caprolactone (PCL) exhibited a reduced toxic effect when compared to emulsions, opening perspectives for these systems to be used as a tool to prolong protection times with lower active repellent concentrations.
Biomimetic calcium carbonate nanoparticles delivered IL-12 mRNA for targeted glioblastoma sono-immunotherapy by ultrasound-induced necroptosis
Authors: Zhao Pengxuan , Tian Yu , Lu Yongping , Zhang Jun , Tao Anyu , Xiang Guangya , Liu Yani
Published: December 2022

Glioblastoma (GBM) is the most aggressive brain tumor, which owns the characteristics of high recurrence, low survival rate and poor prognosis because of the existence of blood brain barrier (BBB) and complicated brain tumor microenvironment. Currently, immunotherapy has attracted much attention on account of favorable therapeutic effect. In this study, we designed a cRGD-modified cancer cell membrane (CM) coated calcium carbonate nanoparticle to deliver interleukin-12 messenger RNA (IL-12 mRNA@cRGD-CM-CaCO3 NPs). The cRGD-modified CM as the shell can endow the nanoparticles with BBB crossing and tumor homing/homotypic targeting effect in the brain tumor microenvironment. IL-12 mRNA-loaded calcium carbonate nanoparticles as the core allow synergistic immunotherapy of necroptosis-induced immune response and IL-12 mRNA transfection under ultrasound irradiation. The as-prepared biomimetic nanoparticles showed superior target and immunotherapeutic outcomes, suggesting that this biomimetic nanoplatform provides a feasible strategy for promoting BBB-penetrating and antitumor immunity.
Synergistic combination of targeted nano-nuclear-reactors and anti-PD-L1 nanobodies evokes persistent T cell immune activation for cancer immunotherapy
Authors: Zhu Lipeng , Li Junnan , Guo Ziang , Kwok Hang Fai , Zhao Qi
Published: December 2022

Background

Antitumor T cell immunotherapy as a novel cancer therapeutic strategy has shown enormous promise. However, the tumor microenvironment (TME) is characterized by the low immunogenicity, hypoxia, and immunosuppressive condition that dramatically limit effective T cell immunotherapy. Thus, an ideal immunotherapy strategy that is capable of reversing the immunosuppressive TME is highly imperative.

Results

In this article, we reported that Fe-doped and doxorubicin (DOX) loaded HA@Cu2−XS-PEG (PHCN) nanomaterials were rationally designed as targeted Fe-PHCN@DOX nano-nuclear-reactors, which evoked persistent T cell immune response together with anti-PD-L1 nanobodies. It was confirmed that nano-nuclear-reactors displayed strong nanocatalytic effect for effective antitumor effects. Consequently, they maximized the immunogenic cell death (ICD) effect for antigen presentation and then stimulated T cell activation. In addition, Fe-PHCN@DOX could reprogram M2-phenotype tumor-associated macrophages (TAMs) into M1-phenotype TAMs by relieving tumor hypoxia. Meanwhile, blockade of the anti-PD-L1 nanobody promoted T cell activation through targeting the PD-1/PD-L1 immunosuppressive pathway. Notably, in vivo tumor therapy verified that this nano-nuclear-reactor could be used as an excellent immunotherapy nanoplatform for tumor eradication and metastasis prevention with nanobody.

Conclusions

Our findings demonstrated that nano-nuclear-reactors in combination with nanobody could evoke persistent T cell immune activation, suggesting them potential as a promising immunotherapy option for reversing immunosuppressive immune-cold tumors.

Graphical Abstract
Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer
Authors: Yang Xiao-Yan , Zhang Jin-Guo , Zhou Qiao-Mei , Yu Jie-Ni , Lu Yuan-Fei , Wang Xiao-Jie , Zhou Jia-Ping , Ding Xin-Fa , Du Yong-Zhong , Yu Ri-Sheng
Published: December 2022

Background

Excessive extracellular matrix (ECM) deposition in pancreatic ductal adenocarcinoma (PDAC) severely limits therapeutic drug penetration into tumors and is associated with poor prognosis. Collagen is the most abundant matrix protein in the tumor ECM, which is the main obstacle that severely hinders the diffusion of chemotherapeutic drugs or nanomedicines.

Methods

We designed a collagenase-functionalized biomimetic drug-loaded Au nanoplatform that combined ECM degradation, active targeting, immune evasion, near-infrared (NIR) light-triggered drug release, and synergistic antitumor therapy and diagnosis into one nanoplatform. PDAC tumor cell membranes were extracted and coated onto doxorubicin (Dox)-loaded Au nanocages, and then collagenase was added to functionalize the cell membrane through lipid insertion. We evaluated the physicochemical properties, in vitro and in vivo targeting, penetration and therapeutic efficacy of the nanoplatform.

Results

Upon intravenous injection, this nanoplatform efficiently targeted the tumor through the homologous targeting properties of the coated cell membrane. During penetration into the tumor tissue, the dense ECM in the PDAC tissues was gradually degraded by collagenase, leading to a looser ECM structure and deep penetration within the tumor parenchyma. Under NIR irradiation, both photothermal and photodynamic effects were produced and the encapsulated chemotherapeutic drugs were released effectively, exerting a strong synergistic antitumor effect. Moreover, this nanoplatform has X-ray attenuation properties that could serve to guide and monitor treatment by CT imaging.

Conclusion

This work presented a unique and facile yet effective strategy to modulate ECM components in PDAC, enhance tumor penetration and tumor-killing effects and provide therapeutic guidance and monitoring.

Graphical Abstract
Metabolomic analysis on the mechanism of nanoselenium alleviating cadmium stress and improving the pepper nutritional value
Authors: Li Dong , Zhou Chunran , Li Jia-Qi , Dong Qinyong , Miao Peijuan , Lin Yongxi , Cheng Haiyan , Wang Yuwei , Luo Luna , Pan Canping
Published: December 2022

Selenium (Se) maintains soil-plant homeostasis in the rhizosphere and regulates signaling molecules to mitigate cadmium (Cd) toxicity. However, there has been no systematic investigation of the effects of nano-selenium (nano-Se) on the regulation of non-target metabolites and nutritional components in pepper plants under Cd stress. This study investigated the effects of Cd-contaminated soil stress and nano-Se (1, 5, and 20 mg/L) on the metabolic mechanism, fruit nutritional quality, and volatile organic compounds (VOCs) composition of pepper plants. The screening of differential metabolites in roots and fruit showed that most were involved in amino acid metabolism and capsaicin production. Amino acids in roots (Pro, Trp, Arg, and Gln) and fruits (Phe, Glu, Pro, Arg, Trp, and Gln) were dramatically elevated by nano-Se biofortification. The expression of genes of the phenylpropane-branched fatty acid pathway (BCAT, Fat, AT3, HCT, and Kas) was induced by nano-Se (5 mg/L), increasing the levels of capsaicin (29.6%), nordihydrocapsaicin (44.2%), and dihydrocapsaicin (45.3%). VOCs (amyl alcohol, linalool oxide, E-2-heptaldehyde, 2-hexenal, ethyl crotonate, and 2-butanone) related to crop resistance and quality were markedly increased in correspondence with the nano-Se concentration. Therefore, nano-Se can improve the health of pepper plants by regulating the capsaicin metabolic pathway and modulating both amino acid and VOC contents.

Graphical Abstract
Profiles and predictive value of cytokines in children with human metapneumovirus pneumonia
Authors: Xiang Wen-qing , Li Lin , Wang Bing-han , Ali Ahmed Faisal , Li Wei
Published: December 2022

Background

Human metapneumovirus (HMPV) is an important cause of respiratory tract infections in young children. Early innate immune response to HMPV is focused on induction of antiviral interferons (IFNs) and other pro-inflammatory cytokines that are critical for the formation of adaptive immune responses. To evaluate the predictive value of Th1/Th2 cytokines which include IL-2, IL-4, IL-6, IL-10, INF-γ and TNF-α in pneumonia caused by HMPV.

Methods

A retrospective study was performed among 59 pneumonia pediatric patients with HMPV infection and 33 healthy children as the control cohort, which was detected by the immunofluorescence assay, and the Th1/Th2 cytokines were measured by flow cytometry. 131 children infected with Influenza virus A (IVA) and 41 children infected with influenza virus B (IVB) were detected by RT-PCR assay in throat swabs.

Results

When compared with the healthy children, children who were infected with HMPV pneumonia had a significantly lower level of IL-2 (p < 0.001) and higher levels of IL-4 (p < 0.001), IL-6 (p = 0.001), IL-10 (p < 0.001), and IFN-γ (p < 0.001). Compared with patients diagnosed with IVA or IVB infection, HMPV-positive patients had significantly higher levels of IL-4 (p < 0.001 and < 0.001), IFN-γ (p < 0.001 and < 0.001), and TNF-α (p < 0.001 and 0.016). Moreover, compared with IVA patients, HMPV-positive patients had a significantly lower level of IL-6 (p = 0.033). Finally, when comparing cytokine levels among the patients with HMPV pneumonia, IL-6 and TNF-α levels were found to be significantly higher in the severe group than the mild group (p = 0.027 and 0.049). The IL-6 and TNF-α were used to differentiate between mild symptoms and severe symptoms in children diagnosed with HMPV pneumonia with an AUC of 0.678 (95% CI 0.526–0.829) and 0.658 (95% CI 0.506–0.809), respectively.

Conclusion

Our study indicated that difference in cytokine trends depending on the virus species. The levels of IL-4, TNF-α and IFN-γ were significantly distinguished in children infected with HMPV versus IVA and IVB. IL-6 and TNF-α may be helpful in assessing the severity and prognosis of HMPV infection.
Coil and n-butyl-2-cyanoacrylate migration into the stomach after TIPS for gastroesophageal variceal bleeding: a case report and literature review
Authors: Zhang Yue-Lin , Nie Chun-Hui , Zhou Tan-Yang , Zhou Guan-Hui , Zhu Tong-Yin , Chen Sheng-Qun , Wang Hong-Liang , Wang Bao-Quan , Yu Zi-Niu , Jing Li , Xia Qi , Chen Hong-Tan , Sun Jun-Hui
Published: December 2022

Background

Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established therapeutic option for the management of variceal hemorrhage in patients with cirrhosis. The simultaneous migration of the coil and n-butyl-2-cyanoacrylate (NBCA) is an extremely rare but significant complication after TIPS. Because of its rare presentation, there are currently no definitive recommendations for the management of this condition.

Case presentation

A 46-year-old man with hepatitis B cirrhosis underwent TIPS placement for uncontrolled gastroesophageal varix (GEV) bleeding secondary to portal hypertension in August 2018. During the procedure, large GEVs were embolized using a coil and NBCA. After a year, coil and NBCA migration into the stomach was observed. Attempts to remove the coil using biopsy forceps during esophagogastroduodenoscopy failed. The patient refused further intervention on the coil to prevent further complications and received conservative therapy instead. Close surveillance with endoscopy is recommended for detecting coils and varices.

Conclusions

The present case reports an extremely rare but significant complication after TIPS, which highlights the management and follow-up recommendation for such rare complications. Our experience may provide guidance for the management of future similar cases and stimulate discussion about treatment methods of similar patients.
Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study
Authors: Shah Bijal D. , Ghobadi Armin , Oluwole Olalekan O. , Logan Aaron C. , Boissel Nicolas , Cassaday Ryan D. , Leguay Thibaut , Bishop Michael R. , Topp Max S. , Tzachanis Dimitrios , O’Dwyer Kristen M. , Arellano Martha L. , Lin Yi , Baer Maria R. , Schiller Gary J. , Park Jae H. , Subklewe Marion , Abedi Mehrdad , Minnema Monique C. , Wierda William G. , DeAngelo Daniel J. , Stiff Patrick , Jeyakumar Deepa , Dong Jinghui , Adhikary Sabina , Zhou Lang , Schuberth Petra C. , Faghmous Imi , Masouleh Behzad Kharabi , Houot Roch
Published: December 2022

Background

Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 CAR T-cell therapy approved in the USA to treat adult patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (R/R B-ALL) based on ZUMA-3 study results. We report updated ZUMA-3 outcomes with longer follow-up and an extended data set along with contextualization of outcomes to historical standard of care.

Methods

Adults with R/R B-ALL received a single infusion of KTE-X19 (1 × 106 CAR T cells/kg). Long-term post hoc subgroup assessments of ZUMA-3 were conducted. Outcomes from matched patients between historical clinical trials and ZUMA-3 patients were assessed in the retrospective historical control study SCHOLAR-3.

Results

After 26.8-months median follow-up, the overall complete remission (CR) rate (CR + CR with incomplete hematological recovery) among treated patients (N = 55) in phase 2 was 71% (56% CR rate); medians for duration of remission and overall survival (OS) were 14.6 and 25.4 months, respectively. Most patients responded to KTE-X19 regardless of age or baseline bone marrow blast percentage, but less so in patients with > 75% blasts. No new safety signals were observed. Similar outcomes were observed in a pooled analysis of phase 1 and 2 patients (N = 78). In SCHOLAR-3, the median OS for treated patients from ZUMA-3 (N = 49) and matched historical controls (N = 40) was 25.4 and 5.5 months, respectively.

Conclusions

These data, representing the longest follow-up of CAR T-cell therapy in a multicenter study of adult R/R B-ALL, suggest that KTE-X19 provides a clinically meaningful survival benefit with manageable toxicity in this population.

Trial Registration: NCT02614066.
The influence of walking speed and effects of signal processing methods on the level of human gait regularity during treadmill walking
Authors: Brachman Anna , Sobota Grzegorz , Bacik Bogdan
Published: December 2022

Background

In recent years the use of sample entropy (SampEn) to evaluate the complexity of the locomotor system in human gait data has gained in popularity. However, it has been suggested that SampEn is sensitive to various input parameters and signal preprocessing methods. This study quantified the effects of different temporal and spatial normalization approaches and various lengths of the template vector (m) on SampEn calculations. The discriminatory ability of SampEn was studied by comparing two walking conditions.

Methods

Twenty-three participants (seven males, 55.7 ± 8.5 years, 165.7 ± 7.9 cm, 80.5 ± 16.7 kg) walked on a treadmill with preferred (Vpref) and maximum (Vmax) speed. Data were segmented and resampled (SEGM), resampled and spatially normalized (NORM), resampled and detrended (ZERO).

Results

For vertical ground reaction force (vGRF) and center of pressure in anterio-posterior direction (COPap), in both walking conditions, SampEn was generally sensitive to the vector length and not to the data processing, except for COPap in ZERO, m = 2, 4. For the COPml SampEn behaved oppositely, it was sensitive to preprocessing method and not to the m length. The regularity of COPap and vGRF in all processed signals increased in Vmax condition. For the COPml only two signals, WHOLE and ZERO, revealed increased complexity caused by more demanding walking conditions.

Conclusions

SampEn was able to discriminate between different walking conditions in all analyzed variables, but not in all signals. Depending on evaluated variable, SampEn was susceptible in different way for the m level and processing method. Hence, these should be checked and selected for each variable independently. For future studies evaluating influence of walking velocity on COP and vGRF regularity during treadmill walking it is advised to use raw time series. Furthermore, to maintain template vector which represents biological relevance it is advised to detect highest frequencies present in analyzed signals and evaluate minimal time interval which can reflect change caused by response of a neuromuscular system. During evaluating treadmill walking measured with 100 Hz sampling frequency it is recommended to adopt m from 6 to 10, when average stride time is up to about 1 s.
Efficient 3D object recognition in mobile edge environment
Authors: Song Mofei , Guo Qi
Published: December 2022

3D object recognition has great research and application value in the fields of automatic drive, virtual reality, and commercial manufacturing. Although various deep models have been exploited and achieved remarkable results for 3D object recognition, their computational cost is too high for most mobile applications. This paper combines edge computing and 3D object recognition into a powerful and efficient framework. It consists of a cloud-based rendering stage and a terminal-based recognition stage. In the first stage, inspired by the cloud-based rendering technique, we upload the 3D object data from the mobile device to the edge cloud server for multi-view rendering. The rendering stage utilizes the powerful computing resource in the edge cloud server to generate multiple view images of the given 3D object from different views by parallel high-quality rendering. During the terminal-based recognition stage, we integrate a lightweight CNN architecture and a neural network quantization technique into a 3D object recognition model based on the multiple images rendered in the edge cloud server, which can be executed fast in the mobile device. To reduce the cost of network training, we propose a novel semi-supervised 3D deep learning method with fewer labeled samples. Experiments demonstrate that our method achieves competitive performance compared to the state-of-the-art methods with low latency running in the mobile edge environment.
Health care systems administrators perspectives on antimicrobial stewardship and infection prevention and control programs across three healthcare levels: a qualitative study
Authors: Aika Isabel Naomi , Enato Ehijie
Published: December 2022

Introduction

Antimicrobial stewardship (AMS) and infection prevention control (IPC) programs are proposed to address antimicrobial resistance. Nigeria’s 5-years action plan for these programs is expiring by 2022. The objective of this study was to examine the perspectives, barriers and facilitators of these programs among health care managers and the current state of these programs in the three levels of healthcare facilities in Benin City, Nigeria.

Methods

Fourteen in-depth interviews were conducted among hospital manager across primary, secondary and tertiary healthcare facilities. The interviews were guided by semi-structured questionnaire. Responses were audio-taped and hand written. Data were analyzed by transcribing recorded tapes into major themes.

Results

Most of the participants viewed inappropriate prescribing as a problem both in the country and their facilities. None of the institutions have a formal AMS program, but participants believed that the presence of drug and therapeutic committee is a foundation for such programme. Majority of the participants acknowledged barriers to AMS to include lack of management backing, interprofessional rivalry, and poor laboratories. Only the tertiary institution has a formal IPC program. Some challenges to IPC across the healthcare institutions are inadequate waste disposal, lack of personal protective equipment and behavioral change among healthcare providers.

Conclusion

There is no AMS program across all facilities studied, although some forms of IPC activities are present in all healthcare institutions, only the tertiary facility has a formal IPC program. Effort should be made to strengthen AMS and IPC in the study facilities.
Antibiotic resistance pattern of microorganisms causing urinary tract infection: a 10-year comparative analysis in a tertiary care hospital of Bangladesh
Authors: Majumder Md. Mahabubul Islam , Mahadi Ashrafur Rahaman , Ahmed Tareq , Ahmed Mostaque , Uddin Mohammad Nazim , Alam Md. Zahirul
Published: December 2022

Background

Antimicrobial resistance is an emerging concern globally in recent years. Management of common infectious diseases like urinary tract infection (UTI) has become challenging. In this context, the purpose of this study is to compare the shifting trends in bacteriology and antibiotic resistance pattern among uropathogens to similar studies conducted at various times in Bangladesh.

Methods

It was a cross-sectional study conducted at the CUMILLA MEDICAL COLLEGE HOSPITAL’S MEDICINE DEPARTMENT in three phases (2011, 2016, 2021. Patients who visited the outpatient and inpatient departments of the study center with symptoms suggestive of a urinary tract infection were undergone urine culture. Those who yielded positive growth in urne culture were finally included in the study.

Results

Escherichia coli(62% in 2021, 86% in 2016 and 76% in 2011) andKlebsiella species(11% in 2021, 10% in 2016 and 11% in 2011) were the most frequently isolated bacteria. Overall, in Gram-negative organisms, resistance was almost > 50% to all the tested antibiotics. Very high frequency of resistance ranging from 66.67 to 93.75% to cotrimoxazole, ciprofloxacin, cefuroxime, cephradine, amoxicillin and nalidixic acid, moderately high resistance to ceftriaxone (64.52%) and gentamicin (53.13%) and low resistance to nitrofurantoin (25.38%) were shown by the most commonly isolated organisms. Resistance to common antibiotics has been significantly increased over time in the isolated orgnaisms, especially in carbapenem and aminoglycoside group.

Conclusion

Resistance of uropathogens against conventional antibiotics used to treat UTI is high and the proportion has been increased over time. The situation might be grave in upcoming years if rational consumption of antibiotics is not warranted.
Lung sparing and ribcage coverage in total body irradiation delivered by helical tomotherapy
Authors: Köksal Mümtaz , Baumert Jonathan , Schoroth Felix , Scafa Davide , Koch David , Leitzen Christina , Sarria Gustavo R. , Giordano Frank A. , Chatzikonstantinou Georgios , Schmeel Leonard C.
Published: December 2022

Purpose

Helical tomotherapy (HT) is a viable method for delivering total body irradiation (TBI) when preparing patients for allogenic stem cell or bone-marrow transplantation. TBI can be planned to reduce the amount of radiation delivered to organs at risk, such as the lungs, with the aim of decreasing toxicity. However, it is important for the ribcage to receive the prescribed radiation dose in preparation for bone-marrow transplantation. In this retrospective study, we analyzed radiation dose coverage of the lungs and ribcage in patients who underwent TBI delivered by HT to achieve lung dose sparing.

Methods

Thirty-five patients were included in the analysis and divided into three groups based on their prescribed radiation dose (4, 8, or 12 Gy). HT was performed using a rotating gantry to reduce radiation to the lungs. Dosimetric parameters for the lungs and ribcage as well as dose-volume histograms were calculated.

Results

The mean lung D95 was 60.97%, 54.77%, and 37.44% of the prescribed dose for patients receiving 4 Gy, 8 Gy, and 12 Gy, respectively. Ribcage coverage was most optimal for patients receiving 4 Gy, with a D95 of 91.27% and mean homogeneity index of 1.17, whereas patients receiving 12 Gy had a mean D95 of 78.65% and homogeneity index of 1.37, which is still within the range recommended by treatment guidelines.

Conclusions

Using HT to achieve lung tissue sparing is a viable approach to minimizing pulmonic complications in patients undergoing TBI. As this planning adjustment does not compromise the dose and quality of coverage received by the ribcage, it is a feasible tool within conditioning regimens for allogeneic bone-marrow transplantation.
A behavior and physiology-based decision support tool to predict thermal comfort and stress in non-pregnant, mid-gestation, and late-gestation sows
Authors: McConn Betty R. , Schinckel Allan P. , Robbins Lindsey , Gaskill Brianna N. , Green-Miller Angela R. , Lay Donald C. , Johnson Jay S.
Published: December 2022

Background

Although thermal indices have been proposed for swine, none to our knowledge differentiate by reproductive stage or predict thermal comfort using behavioral and physiological data. The study objective was to develop a behavior and physiology-based decision support tool to predict thermal comfort and stress in multiparous (3.28 ± 0.81) non-pregnant (n = 11), mid-gestation (n = 13), and late-gestation (n = 12) sows.

Results

Regression analyses were performed using PROC MIXED in SAS 9.4 to determine the optimal environmental indicator [dry bulb temperature (TDB) and dew point] of heat stress (HS) in non-pregnant, mid-gestation, and late-gestation sows with respiration rate (RR) and body temperature (TB) successively used as the dependent variable in a cubic function. A linear relationship was observed for skin temperature (TS) indicating that TDBrather than the sow HS response impacted TSand so TSwas excluded from further analyses. Reproductive stage was significant for all analyses (P < 0.05). Heat stress thresholds for each reproductive stage were calculated using the inflections points of RR for mild HS and TBfor moderate and severe HS. Mild HS inflection points differed for non-pregnant, mid-gestation, and late gestation sows and occurred at 25.5, 25.1, and 24.0 °C, respectively. Moderate HS inflection points differed for non-pregnant, mid-gestation, and late gestation sows and occurred at 28.1, 27.8, and 25.5 °C, respectively. Severe HS inflection points were similar for non-pregnant and mid-gestation sows (32.9 °C) but differed for late-gestation sows (30.8 °C). These data were integrated with previously collected behavioral thermal preference data to estimate the TDBthat non-pregnant, mid-gestation, and late-gestation sows found to be cool (TDB < TDBpreference range), comfortable (TDB = TDBpreference range), and warm (TDBpreference range < TDB < mild HS).

Conclusions

The results of this study provide valuable information about thermal comfort and thermal stress thresholds in sows at three reproductive stages. The development of a behavior and physiology-based decision support tool to predict thermal comfort and stress in non-pregnant, mid-gestation, and late-gestation sows is expected to provide swine producers with a more accurate means of managing sow environments.
Future of work in 2050: thinking beyond the COVID-19 pandemic
Authors: Barbosa Carlos Eduardo , de Lima Yuri Oliveira , Costa Luis Felipe Coimbra , dos Santos Herbert Salazar , Lyra Alan , Argôlo Matheus , da Silva Jonathan Augusto , de Souza Jano Moreira
Published: December 2022

Work has been continuously changing throughout history. The most severe changes to work occurred because of the industrial revolutions, and we are living in one of these moments. To allow us to address these changes as early as possible, mitigating important problems before they occur, we need to explore the future of work. As such, our purpose in this paper is to discuss the main global trends and provide a likely scenario for work in 2050 that takes into consideration the recent changes caused by the COVID-19 pandemic. The study was performed by thirteen researchers with different backgrounds divided into five topics that were analyzed individually using four future studies methods: Bibliometrics, Brainstorming, Futures Wheel, and Scenarios. As the study was done before COVID-19, seven researchers of the original group later updated the most likely scenario with new Bibliometrics and Brainstorming. Our findings include that computerization advances will further reduce the demand for low-skill and low-wage jobs; non-standard employment tends to be better regulated; new technologies will allow a transition to a personalized education process; workers will receive knowledge-intensive training, making them more adaptable to new types of jobs; self-employment and entrepreneurship will grow in the global labor market; and universal basic income would not reach its full potential, but income transfer programs will be implemented for the most vulnerable population. Finally, we highlight that this study explores the future of work in 2050 while considering the impact of the COVID-19 pandemic.
Health-Related Quality of Life in pre-dialysis patients with chronic kidney disease: the role of Big-Five personality traits and illness denial
Authors: Pugi Daniele , Ferretti Fabio , Galeazzi Maddalena , Gualtieri Giacomo , Lorenzi Lore , Pappalardo Niccolò , Macrì Pasquale Giuseppe , Garosi Guido , Coluccia Anna , Pozza Andrea
Published: December 2022

Background

Health-Related Quality of Life (HRQoL) in patients with chronic kidney disease (CKD) is significantly affected, regardless of the stage of the disease, as regards the physical, psychological and social functioning dimension. Big-Five personality traits can affect patients’ HRQoL and willingness to take treatment options. Illness denial consists of denial of negative emotions, resistance to change and conscious avoidance. Poorer HRQoL can predict a higher risk of hospitalization and mortality, and broadly a worse adjustment to the dialytic therapy. Thus, a clearer knowledge of the psychological variables associated with a worse HRQoL in the predialysis stage might improve the intervention planning. No study investigated illness denial and personality traits simultaneously. We investigated the role of illness denial and Big-Five personality traits in the domains of HRQoL in predialysis patients with CKD.

Methods

One hundred adults (mean age: 75.87 years) with CKD participated. The Kidney Disease Quality of Life Short form, the Italian version of Ten Item Personality Inventory Revised, the Illness Denial Questionnaire, and the State-Trait Anxiety Inventory Form-Y were administered.

Results

Illness denial was associated with increased HRQoL related to symptoms/problems, effect and burden of CKD and cognitive functions domains, and it was a predictor of higher HRQoL in the last three domains mentioned above. Extraversion was related to better work status and sexual function; agreeableness was linked to elevated cognitive function, quality of social interaction and sexual function; conscientiousness was related to better sexual function; neuroticism was linked to improved cognitive and sexual functions; in the end, openness to experience was related to fewer symptoms and problems.

Conclusions

This is the first study which simultaneously assessed Big-Five personality traits and illness denial in different domains of HRQoL of CKD patients. Personalised psychological interventions aimed at improving HRQoL in this population might focus on specific illness denial processes and personality traits.