bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibody response, neutralizing potency, and transplacental antibody transfer following SARS‐CoV‐2 infection versus mRNA‐1273, BNT162b2 COVID‐19 vaccination in pregnancy
Authors: Dude Carolynn M. , Joseph Naima T. , Forrest Alexandra D. , Verkerke Hans P. , Cheedarla Narayanaiah , Govindaraj Sakthivel , Irby Les’Shon S. , Easley Kirk A. , Smith Alicia K. , Stowell Sean R. , Neish Andrew , Amara Rama Rao , Jamieson Denise J. , Dunlop Anne L. , Badell Martina L. , Velu Vijayakumar
Published: January 2023

Objective

To improve our understanding of the immune response, including the neutralization antibody response, following COVID‐19 vaccination in pregnancy.

Methods

This was a prospective cohort study comprising patients with PCR‐confirmed SARS‐CoV‐2 infection and patients who received both doses of mRNA COVID‐19 vaccine (mRNA‐1273, BNT162b2) in pregnancy recruited from two hospitals in Atlanta, GA, USA. Maternal blood and cord blood at delivery were assayed for anti‐receptor binding domain (RBD) IgG, IgA and IgM, and neutralizing antibody. The detection of antibodies, titers, and maternal to fetal transfer ratios were compared.

Results

Nearly all patients had detectable RBD‐binding IgG in maternal and cord samples. The vaccinated versus infected cohort had a significantly greater proportion of cord samples with detectable neutralizing antibody (94% vs. 28%, P < 0.001) and significantly higher transfer ratios for RBD‐specific IgG and neutralizing antibodies with a transfer efficiency of 105% (vs. 80%, P < 0.001) and 110% (vs. 90%, P < 0.001), respectively. There was a significant linear decline in maternal and cord blood RBD‐specific IgG and neutralizing antibody titers as time from vaccination to delivery increased.

Conclusions

Those who receive the mRNA COVID‐19 vaccine mount an immune response that is equivalent to—if not greater than—those naturally infected by SARS‐CoV‐2 during pregnancy.
Pediatric cystine stone successfully treated by mini‐percutaneous nephrolithotripsy and antegrade ureteroscopy
Authors: Kakinoki Hiroaki , Yamaguchi Yukako , Kakinoki Yuka , Udo Kazuma , Tobu Shohei , Noguchi Mitsuru
Published: January 2023

Introduction

Cystinuria is often diagnosed by large renal stone for pediatric patients. The patients suffer from recurrence of stone disease, develop the chronic kidney disease and fall into end‐stage renal failure. Total removal of stone at the first intervention and prevention of recurrence are essential. Although, it is difficult to treat the pediatric stone patients for their anatomical feature.

Case presentation

We report three cases of pediatric cystine stone patients (two 4‐year‐old boys and a 9‐year‐old girl) successfully treated by mini‐percutaneous nephrolithotripsy and antegrade ureteroscopy. We could remove stones completely in all three cases, and the patients did not suffer from major complications.

Conclusion

It is essential to select the surgical approach, the endourological device, and the patient's position which is suitable for the age, the body size, and the condition of stones at the initial intervention of pediatric cystine stone.
Framework nucleic acids directed assembly of Au nanostructures for biomedical applications
Authors: Liu Bing , Qi Zhonglin , Chao Jie
Published: January 2023

Au nanostructures have elicited considerable interest because of their unique optical and physicochemical properties. These characteristics are mostly depended on the size, shape, chemical composition and dielectric environment of Au nanoparticles (AuNPs). Because of the easy chemical modification and programmable design of DNA molecules, they can not only combine to the surface of AuNP for improved stability, but also form the framework nucleic acids (FNAs) for direct assembly of different Au nanostructures with precise configuration and multiple dimensions. This paper starts with the synthesis and properties of Au nanomaterials. Followed by a brief introduction to the development of FNA nanotechnology, the FNA‐directed assembly of Au nanostructures is discussed. Then, we focus on the biomedical applications of these Au nanostructures, including biosensing and therapeutics. In the end, we envision an insight into the remaining challenges and future perspectives toward FNA‐based metal functional materials.
Performance assessment of subsurface drainage systems in the Harran Plain of the South‐East Anatolian region of Turkey
Authors: Güngör Kamil , Bahçeci Barış
Published: January 2023

The purpose of performance assessment of subsurface drainage systems is to achieve efficient and effective system performance by providing relevant feedback to the management of the drainage system at all levels. Therefore, it assists management in determining whether performance is satisfactory and, if not, what corrective actions need to be taken and where to rectify the situation. In this study, approximately 30% of the drainage systems built in the Harran Plain were monitored during one irrigation season in 2017. The fluctuation of the water table was measured daily at a total of 33 subcentres. In addition, electrical conductivity (EC) and pH values were measured by taking water samples from six collectors once a week. Drain flow measurements were carried out at three collector outlets. According to the SEW30 (sum of excess water at depths less than 30 cm) indicator, 82% of the monitored areas had good, medium‐good drainage and moderate drainage. The seasonal average water table depth of the monitored area was found to be approximately 120 cm. The data show the existence of a drainage system that creates an aerated soil layer suitable for all shallow‐ and deep‐rooted, water‐resistant, and sensitive plants in all of the monitored areas. Generally, the salinity of drainage water is much higher than that of irrigation water. This value was up to 25 times higher in some collector outlets. This finding has raised suspicions that salty groundwater is being pumped into the drainage system.
The roles of proteases in prostate cancer
Authors: Koistinen Hannu , Kovanen Ruusu‐Maaria , Hollenberg Morley D. , Dufour Antoine , Radisky Evette S. , Stenman Ulf‐Håkan , Batra Jyotsna , Clements Judith , Hooper John D. , Diamandis Eleftherios , Schilling Oliver , Rannikko Antti , Mirtti Tuomas
Published: January 2023

Since the proposition of the pro‐invasive activity of proteolytic enzymes over 70 years ago, several roles for proteases in cancer progression have been established. About half of the 473 active human proteases are expressed in the prostate and many of the most well‐characterized members of this enzyme family are regulated by androgens, hormones essential for development of prostate cancer. Most notably, several kallikrein‐related peptidases, including KLK3 (prostate‐specific antigen, PSA), the most well‐known prostate cancer marker, and type II transmembrane serine proteases, such as TMPRSS2 and matriptase, have been extensively studied and found to promote prostate cancer progression. Recent findings also suggest a critical role for proteases in the development of advanced and aggressive castration‐resistant prostate cancer (CRPC). Perhaps the most intriguing evidence for this role comes from studies showing that the protease‐activated transmembrane proteins, Notch and CDCP1, are associated with the development of CRPC. Here, we review the roles of proteases in prostate cancer, with a special focus on their regulation by androgens.
Injectable cell‐laden hybrid bioactive scaffold containing bioactive glass microspheres
Authors: Rahimnejad Maedeh , Charbonneau Cindy , He Zinan , Lerouge Sophie
Published: January 2023

The rising incidence of bone disorders has resulted in the need for minimally invasive therapies to meet this demand. Injectable bioactive filler, alone or with cells, could be applied in a minimally invasive manner to fulfill irregular cavities in non‐load bearing sites, which do not require high mechanical properties. Thermosensitive chitosan hydrogels that transition from a liquid to a mechanically stable solid at body temperature provide interesting features as in‐situ injectable cytocompatible biomaterials, but they are not osteoconductive. Osteoconductivity can be applied in combination with bioactive ceramics e.g., 45S5‐Bioglass® (BG). However, BG addition in chitosan hydrogels results in pH elevation, due to rapid ions release, which adversely affects gel formation, mechanical properties, and cytocompatibility. To address this, we created hybrid hydrogels, where BG is concentrated in chitosan‐based microbeads, incorporated in in‐situ gelling chitosan hydrogels. We then compared the hybrid hydrogels' properties to chitosan hydrogels with homogenously distributed BG. By varying the stirred emulsification process, BG percentage, and CH formulation, we could tune the microbeads' properties. Incorporation of BG microbeads drastically improved the hydrogel's compressive modulus in comparison to homogeneously distributed BG. It also strongly increased the survival and metabolic activities of encapsulated cells. Calcium/phosphate increase on BG microbeads suggests hydroxyapatite formation. The small diameter of microbeads allows minimally invasive injection through small needles. The feasibility of freezing and thawing microbeads provides the possibility of long‐term storage for potential clinical applications. These data indicate that this hybrid hydrogel forms a promising injectable cell‐laden bioactive biomaterial for the treatment of unloaded bone defects.
Hsa_circ_0001944 enhanced GSPT1 expression via sponging miR‐498 to promote proliferation and invasion of gastric cancer
Authors: Liu Rujiao , Han Xiaotian , Gao Shuiping , Chen Yang , Zhang Jian
Published: January 2023

Background

Gastric cancer (GC) is the fifth most common malignant tumor and the third leading cause of cancer‐related deaths worldwide. CircRNAs may provide new insights into the development of GC by acting as oncogenes or tumor suppressors. In this study, we aim to examine the biological role of hsa_circ_0001944 (circFIRRE) in tumor progression of GC.

Methods

The bioinformatic analysis, qPCR, Western blotting, and immunohistochemistry were fulfilled to detect the expression of hsa_circ_0001944, miR‐498, and GSPT1 in gastric cancer. Gain or loss of function approaches were used to investigate the biological functions of hsa_circ_0001944. MTS, EDU, wound healing, and transwell assays were performed to study the proliferation, invasion, and migration of GC cells. These molecular mechanisms were detected by luciferase reporter assays and chromatin immunoprecipitation assays.

Results

We screened out hsa_circ_0001944, whose expression was significantly increased in gastric cancer tissues. Knockdown of hsa_circ_0001944 significantly suppressed the cell proliferation, invasion, and migration. Mechanistic investigations showed that hsa_circ_0001944 can bind to and sponge miR‐498. Moreover, hsa_circ_0001944 sponged miR‐498 to increase GSPT1 expression, thereby promoted excessive proliferation and maintained the malignant phenotype of GC cells.

Conclusion

The present study demonstrates the hsa_circ_0001944/miR‐498/GSPT1 axis contributes to GC development. This may provide a target for GC therapy and potential prognostic biomarker.
Silencing circUSP48 suppresses osteosarcoma progression by regulating the miR‐335/ smad nuclear interacting protein 1 pathway
Authors: Luo Yue , Yang Bo , Yuan Xiaopin , Zheng Jian
Published: January 2023

Background

Circular RNAs (circRNAs) can have a critical function in the multi‐processes of osteosarcoma (OS). Nevertheless, whether circUSP48 is involved in OS progression remains unclear.

Methods

In the current work, the expression of circUSP48, miR‐335 and SNIP1 in OS cell lines and tissues were evaluated using qRT‐PCR. Then, Sanger sequencing, RNase R treatment and FISH assay were performed for circUSP48 validation. Furthermore, the function and potential mechanisms of circUSP48 in OS were investigated by performing loss‐of‐function experiments.

Results

Silencing circUSP48 could suppress proliferation, invasion as well as migration of OS cells in vitro, also inhibiting the growth of tumor in vivo. Importantly, circUSP48 promoted OS malignancy by sponging miR‐335 to upregulate SNIP1.

Conclusion

Overall, these findings suggested that circUSP48 acted as an oncogene in OS, which might become a new target for OS therapy.
Comprehensive analysis of aberrantly expressed circRNAs, mRNAs and lncRNAs in patients with nasopharyngeal carcinoma
Authors: Guo Feifan , Chen Dayang , Zong Zengyan , Wu Wei , Mo Chan , Zheng Zhou , Li Jian , Zhang Xiuming , Xiong Dan
Published: January 2023

Background

The location of nasopharyngeal cancer is hidden, so it is difficult to diagnose at an early stage. In this study, we aimed to investigate the expression profiles of circRNAs, mRNAs and IncRNAs and to provide some basis for further studies.

Methods

Expression profiles of circRNAs, mRNAs, and lncRNAs were analyzed using microarray techniques. The differentially expressed ncRNA was calculated by bioinformatics.

Results

A total of 3048 circRNAs, 2179 lncRNAs, and 2015 mRNAs were detected to be significantly differentially expressed in NPC. The most upregulated circRNAs, lncRNAs, and mRNAs were hsa‐circ‐0067562, NONHSAT232922.1, and HOXB13, respectively. And, the most downregulated circRNAs, lncRNAs, and mRNAs were hsa_circ_0078837, lnc‐TTC8‐4:3, and LTF, respectively. The number of upregulated DE lncRNAs was more than twice than those downregulated. Our data showed that 80.44% of pairs of lncRNAs and cis‐mRNAs demonstrated positive correlations. For lncRNAs and trans‐mRNAs pairs, 53.7% of pairs showed positive correlation. LncRNA‐mediated cis regulation is a prevalent regulatory mode in the development of nasopharyngeal carcinoma. CR1, LRMP and SORBS2 are predicted to be mediated not only by cis‐acting lncRNA modes of action, but also by trans‐acting lncRNA mechanisms. Additionally, we constructed a diagnostic prediction model with a high sensitivity and specificity.

Conclusion

Our study characterized the landscape of circRNAs, mRNAs and lncRNAs in NPC tissue and provided novel insights into the molecular mechanisms of NPC.
Population Pharmacokinetic and Exposure–Safety Analyses of Ibrutinib for the Treatment of Chronic Graft‐Versus‐Host Disease
Authors: Ogawa Tetsuro , Mita Sachiko , Atluri Harisha , Iwaki Yuki
Published: January 2023

The population pharmacokinetic (PK) and exposure–response (E–R) analyses for the safety of ibrutinib for the treatment of chronic graft‐versus‐host disease (cGVHD) is presented. This work aims to develop a population PK model for ibrutinib based on data from clinical studies in subjects with cGVHD, to evaluate the impact of intrinsic and extrinsic factors on PK parameters as well as systemic exposure levels, and to assess an E–R relationship for selected safety end points. Pooled data from 162 subjects with cGVHD enrolled in 4 clinical studies were included in the population PK analysis. In the studies, an ibrutinib dose of 420 mg once daily was administered orally. With the exception of 1 study, the study protocols instructed for a reduction of the ibrutinib dose to 140 or 280 mg once daily, depending on concomitant CYP3A inhibitor use. Concomitant CYP3A inhibitor use was found to be a primary covariate for relative bioavailability (F1): the F1 value increased 2.22‐fold with concomitant moderate CYP3A inhibitors and 3.09‐fold with concomitant strong CYP3A inhibitors, compared with the F1 value in the absence of CYP3A inhibitors. In addition, Japanese ethnicity led to an F1 value that was 1.70‐fold higher than that in the non‐Japanese population. Simulations using the final PK model suggest that ibrutinib exposure was appropriately controlled within the therapeutic range in the entire cGVHD population by applying dose reductions depending on the use of CYP3A inhibitors, and that additional dose modification for the Japanese population would not be required. The subsequent E–R analysis suggests no apparent association between the systemic exposure to ibrutinib and the selected safety end points.
Introducing dental students to dental public health: An analysis of US predoctoral course syllabi
Authors: McKernan Susan C. , Sukalski Jennifer M. C. , Starman Emily E. , Mayhle Miriam M. , Holland Haley A. , Chi Donald L.
Published: January 2023

Dental public health competencies in predoctoral dental education ensure that students have the skills to succeed in an increasingly complex professional environment. This study examined existing public health curricula in US dental education and their alignment with national recommendations from the American Association of Public Health Dentistry (AAPHD) and guidance from the Healthy People Curriculum Task Force for health professions education programs. We contacted all US dental schools (N = 66) in November 2020–January 202 and requested syllabi for schools’ first course with dental public health content. We received 34 syllabi, which provided textual data for content analysis. The authors used an initial content analysis tool to extract descriptive course characteristics. Then, direct and emergent coding was performed to summarize course content. Direct codes included the 23 dental public health topics specified by AAPHD recommendations. Uncategorized content was coded using an inductive approach to identify emergent course themes. Frequently covered topics included principles of dental public health (79% of syllabi) and access to care (79%). “Health disparities” was the most common emergent theme, with 50% of courses including related content. There was little consistency in how courses approached each topic. For example, the topic “access to care” covered healthcare delivery systems, determinants of health, legislative reform, and advocacy. Dental public health was often taught alongside unrelated content. Recommendations for dental public health competencies should be updated to include new educational priorities, align with current national recommendations, and align with Commission on Dental Accreditation Standards more clearly.
Prophylactic tenofovir alafenamide for hepatitis B virus reactivation and reactivation‐related hepatitis
Authors: Suda Goki , Baba Masaru , Yamamoto Yoshiya , Sho Takuya , Ogawa Koji , Kimura Megumi , Hosoda Shunichi , Yoshida Sonoe , Kubo Akinori , Fu Qingjie , Yang Zijian , Tokuchi Yoshimasa , Kitagataya Takashi , Maehara Osamu , Ohnishi Shunsuke , Yamada Ren , Ohara Masatsugu , Kawagishi Naoki , Natsuizaka Mitsuteru , Nakai Masato , Morikawa Kenichi , Furuya Ken , Suzuki Kazuharu , Izumi Takaaki , Meguro Takashi , Terashita Katsumi , Ito Jun , Kobayashi Tomoe , Tsunematsu Izumi , Sakamoto Naoya
Published: January 2023

No prospective study on the efficacy of tenofovir alafenamide (TAF), a novel tenofovir prodrug, in preventing hepatitis B virus (HBV) reactivation has yet been reported. This multicenter prospective study enrolled HBV‐carriers who received TAF to prevent HBV reactivation before antitumor or immunosuppressive therapy, and patients with resolved HBV infection who experienced HBV‐reactivation and received TAF to prevent HBV reactivation‐related hepatitis. The efficacy of prophylactic TAF in preventing HBV reactivation and HBV reactivation‐related hepatitis was evaluated at 6 and 12 months after initiating TAF. Overall, 110 patients were administered TAF to prevent HBV reactivation or HBV reactivation‐related hepatitis. Three patients died owing to primary disease, whereas one patient was transferred to another hospital within 6 months after initiating TAF. Seven patients died due to primary disease, and five patients were transferred to another hospital within 12 months after initiating TAF. Therefore, 106 and 94 (77 patients with HBV infection, 17 with previous‐HBV infection) patients were evaluated at 6 and 12 months after initiating TAF, respectively. No patient experienced HBV reactivation, HBV reactivation‐related hepatitis, or treatment discontinuation due to HBV reactivation or adverse events of TAF after 6 and 12 months. TAF could effectively prevent HBV reactivation and HBV reactivation‐related hepatitis.
Local immune dysregulation and subsequent inflammatory response contribute to pulmonary edema caused by Enterovirus infection in mice
Authors: Sun Tiantian , Li Dong , Dai Xinchen , Meng Caiyun , Li Yi , Cheng Cheng , Ji Wangquan , Zhu Peiyu , Chen Shuaiyin , Yang Haiyan , Jin Yuefei , Zhang Weiguo , Duan Guangcai
Published: January 2023

Pulmonary edema that comes on suddenly is the leading cause of mortality in hand‐foot‐and‐mouth disease (HFMD) patients; however, its pathogenesis is still largely unclear. A range of research suggest immunopathogenesis during the occurrence of pulmonary edema in severe HFMD patients. Herein, to investigate the potential mechanism of immune dysregulation in the development of pulmonary edema upon Enterovirus (EV) infection, we established mouse infection models for Enteroviruses (EVs) including Coxsackievirus (CV) A6, Enterovirus A71 (EVA71), and CVA2 exhibiting a high incidence of pulmonary edema. We found that EVs infection induced an immune system disorder by reducing the numbers of pulmonary and circulatory T cells, B cells, macrophages, and monocytes and increasing the numbers of lung neutrophils, myeloid‐derived suppressor cells (MDSCs), and activated T cells. In addition, the concentrations of C−X−C motif chemokine ligand 1 (CXCL‐1), tumor necrosis factor‐alpha, monocyte chemoattractant protein‐1, and interleukin 6 were increased in EV‐infected lungs. Moreover, we found that EVs replication in mice lungs lead to apoptosis of lung cells and degradation of tight junction proteins. In conclusion, EVs infection likely triggered a complexed immune defense mechanism and caused dysregulation of innate immune cells (MDSCs, neutrophils, monocytes, and macrophages) and adaptive cellular immunity (B cells, T cells). This dysregulation increased the release of cytokines and other inflammatory factors from activated immune‐related cells and caused lung barrier damage and pulmonary edema.
Association between trans fatty acids and COVID‐19: A multivariate Mendelian randomization study
Authors: Liu Xuxu , Du Zhiwei , Wang Jing , Wang Qiang , Zheng Yi , Niu Le , Hao Chenjun , Xue Dongbo , Zhang Yingmei
Published: January 2023

Traditional observational studies have suggested a potential association between trans fatty acids (TFAs), which are considered to be health‐damaging fatty acids, and coronavirus disease 2019 (COVID‐19). However, whether there is a causal relationship between them is currently unclear. We aimed to investigate the causal link between genetically determined TFAs and COVID‐19. We performed univariate and multivariate Mendelian randomization (MR) studies using summary statistics from the European Pedigree TFAs (n = 8013), COVID‐19 susceptibility (n = 159 840), COVID‐19 hospitalization (n = 44 986), and COVID‐19 severity (n = 18 152) genome‐wide association studies (GWAS). The inverse variance weighted (IVW) method was used as the primary MR analysis, and several other methods were used as supplements. In univariate MR analysis, higher levels of circulating trans, cis‐18:2 TFAs were positively associated with a higher COVID‐19 hospitalization rate (p < 0.0033; odds ratio [OR] = 1.637; 95% confidence interval [CI]: 1.116–2.401) and COVID‐19 severity (p < 0.0033; OR = 2.575; 95% CI: 1.412–4.698). Furthermore, in multivariate MR analysis, trans, cis‐18:2 had an independent and significant causal association with a higher COVID‐19 hospitalization rate (p = 0.00044; OR = 1.862; 95% CI = 1.316–2.636) and COVID‐19 severity (p = 0.0016; OR = 2.268; 95% CI = 1.361–3.779) after the five TFAs were adjusted for each other. Together, our findings provide evidence that trans, cis‐18:2 TFAs have an independent and robust causal effect on COVID‐19 hospitalization and severity.
First report of coinfection and whole‐genome sequencing of norovirus and sapovirus in an acute gastroenteritis patient from Pakistan
Authors: Umair Massab , Rehman Zaira , Haider Syed Adnan , Usman Muhammad , Rana Muhammad Suleman , Ikram Aamer , Salman Muhammad
Published: January 2023

Acute gastroenteritis is one of the most common diseases in infants and children in developing countries including Pakistan. In Pakistan, rotavirus (RVA) is known to contribute significantly to pediatric diarrheal illness, but the contribution of other viruses is still unclear. In the current study we have identified a case of mixed infection of norovirus (NoV) and sapovirus (SaV) in a 2‐year‐old child with acute gastroenteritis. The sample was initially processed for the detection of group A RVA through ELISA followed by NoV using RT‐PCR assay. The sample tested positive for NoV RNA and was later subjected to whole‐genome sequencing using meta‐genome approach on Miseq (Illumina) platform. Sequencing results revealed GII.15 genotype of NoV that clustered with viruses from China and USA from 2017 to 2021. We also retrieved the complete genome of SaV (GI.1 genotype) from the same sample and phylogenetic analysis showed clustering with strains reported from Japan, South Korea, US, and Taiwan during 2012−2016. This is the first report from Pakistan that confirms coinfection of NoV and SaV and elucidates their whole genomes. We recommend initiation of NoV and SaV surveillance program to ascertain disease burden and explore genetic diversity, especially as RVA vaccines have been included in national immunization program.
Antibiotic release from PMMA spacers and PMMA beads measured with ELISA: Assessment of in vitro samples and drain fluid samples of patients
Authors: Janssen Daniël M. C. , Willems Paul , Geurts Jan , Arts Chris J. J.
Published: January 2023

For prosthetic joint infections, antibiotic loaded poly methyl methacrylate (PMMA) spacer or beads can be used to release high concentrations of antibiotics locally at the infection site, while minimizing systemic toxicity. The aim of this study is to determine in vitro and in vivo pharmacokinetic release profile of antibiotics from PMMA spacers and PMMA beads. For the in vitro experiment, the PMMA spacers or beads were submerged in phosphate‐buffered saline and gentamicin concentrations were determined from collected specimen at several times points, measured with enzyme‐linked immunosorbent assays (ELISA). To assess the in vivo antibiotic release profile of different spacers, wound drainage fluid samples were collected after implantation of a spacer over a period of maximum 14 days. After 48 h, the burst gentamicin concentration elution was 9862 ± 1782 ng/ml (mean ± SD) from spacers versus 38,394 ± 7071 ng/ml (mean ± SD) for beads. Over 35 days, spacers had eluted a cumulative mean concentration of 13,812 ± 3548 versus 55,048 ± 12,006 ng/ml for beads (p < 0.001). Clinical samples of patients with a Vancogenx® spacer showed higher gentamicin release than Refobacin™ spacers (p < 0.001). This is the first study that measured the release data of local antibiotics with ELISA. Compare to spacers, the exact release values of gentamicin from PMMA beads are more than 10 times higher and reached a maximum much later than spacers. This makes the use of PMMA beads more preferable to use for treatment of the infection itself.
In search of better snacks: ohmic‐heating nixtamalized flour and amaranth addition increase the nutraceutical and nutritional potential of vegetable‐enriched tortilla chips
Authors: Domínguez‐Hernández Elisa , Gutiérrez‐Uribe Janet A. , Domínguez‐Hernández Martha E. , Loarca‐Piña Guadalupe F. , Gaytán‐Martínez Marcela
Published: January 2023

BACKGROUND

Nixtamalized flour snacks such as tortilla chips are widely consumed across the world, but they are nutritionally poor and contribute to obesity and other non‐communicable diseases. The production of healthy versions of such snacks, by incorporating vegetables and improving the quality of the flours used in their formulation, could help address these nutritional challenges. This study compared the fortification of baked tortilla chips with vegetable leaf powders (kale and wild amaranth at 0%, 4%, 8%, and 16% w/w) and using two types of nixtamalized flour: traditional (TNF) and with ohmic heating (OHF).

RESULTS

Overall, the use of OHF increased 1.88 times the fibre in enriched and non‐enriched snacks with respect to TNF, but the latter had 1.85 times more protein. Addition of 16% of vegetable powders increased protein (kale = 1.4‐fold; amaranth = 1.3‐fold) and dietary fibre (kale = 1.52‐fold; amaranth = 1.7‐fold). Amaranth enrichment improved total phenolic content (TPC) and total flavonoid content (TFC) of chips at least 1.2 and 1.63 times, respectively. OHF chips also had higher bound TPC than TNF ones, regardless of vegetable addition. Combinations of OHF with 16% amaranth produced chips 1.74‐fold higher in antioxidant capacity than non‐enriched ones, due to increased content of phenolics such as ferulic acid.

CONCLUSION

This work showed that tortilla chips made using nixtamalized flour produced with assisted ohmic heating, alone or in combination with wild amaranth leaf powder, could be used in the production of healthy maize snacks to enhance their prospective antioxidant activity and nutritional value. © 2023 Society of Chemical Industry.
Deterministic and stochastic analysis of a modified Leslie–Gower predator–prey model with Holling‐type II functional response
Authors: Xu Chaoqun , Ke Zhihao
Published: January 2023

This paper aims to study the deterministic and stochastic features of a modified Leslie–Gower predator–prey model with Holling‐type II functional response. We first investigate the dynamical properties of the deterministic model, including existence and stability of the equilibrium, and different types of bifurcations. For the stochastic model, a phenomenon of noise‐induced state transition is found. By applying the stochastic sensitivity functions technique, we construct the confidence domain of stochastic attractor and then estimate the critical value of the intensity of noise generating this transition. Numerical simulations are performed to validate the analytical findings.
Research on the 2‐D annular leaky‐wave antenna
Authors: Huo Xingying , Li Zheng
Published: January 2023

This paper studies a 2‐D planar periodic leaky‐wave antenna based on a series of concentric annular microstrip rings on a grounded dielectric slab. The leaky wave is generated from the perturbation to the surface wave, which is excited from the fundamental and dominant TM0 mode. The computation method for the propagation constant is first analyzed, and then the radiation property is researched. A set of suitable structural parameters for only −1th spacial harmonic radiation are extracted from the theoretical computation and then verified by the simulation, which shows an agreement. The results indicate that this proposed antenna can radiate two symmetrical flat conical beams with over 90% total efficiency. The theoretical results on radiation performance are then verified by simulation and measurement with good agreement.
A compact lumped‐element two‐way differential to single‐ended Wilkinson power combiner with embedded impedance transformation
Authors: Zhang Zhenyi , Zhao Zihan , Ye Zonglin , Xie Qian , Wang Zheng
Published: January 2023

This letter presents a compact lumped‐element two‐way differential to single‐ended Wilkinson power combiner with embedded impedance transformation. It consists of two transformer baluns and two parallel resistance and capacitor (RC) branches. The two transformers generate high‐order impedance transformation networks at even‐mode operation and form resonators together with the two parallel RC branches at odd‐mode operation, thus achieving broadband impedance matching and power combining with a compact area. A proof‐of‐concept prototype working at 1.7 GHz is designed and fabricated. Measurement results show that the peak isolation is 24.5 dB, insertion loss is from 0.34 to 1.15 dB and magnitude and phase imbalance are within 0.1 dB and , respectively, over the frequency range from 1.37 to 1.97 GHz. The area is only 6.54 mm  6 mm.
Developing and validating an integrated instrument for nursing assessments in adult hospitalization units: Study protocol
Authors: Luna‐Aleixos David , González‐Chordá Víctor M. , Aquilué‐Ballarí Marta , Llagostera‐Reverter Irene , Mecho‐Montoliu Gema , Cervera‐Gasch Águeda , Valero‐Chillerón María Jesús , Mena‐Tudela Desirée , Andreu‐Pejó Laura
Published: January 2023

Aims

To develop and validate an instrument that integrates functional capacity, risk of pressure ulcers and risk of falling with a more parsimonious approach towards nursing assessments in hospitalization units.

Design

Cross‐sectional validation multicentre study.

Methods

Socio‐demographic variables and assessments of Barthel Index, Braden Index and Downton Scale are included via electronic health records. Instrument's development process will include: (i) conceptual assessments; (ii) content validity; (iii) construct validity; (iv) internal consistency and (v) interobserver reliability. The analysis will consider possible differences in medical and surgical hospitalization units, hospitalization type or being a COVID‐19 patient. This study was accepted for funding in November 2020 and approved by the Ethics and Research Committee in January 2021.

Results

An integrated instrument that lowers the administrative load of nursing assessments and allows at‐risk patients to be detected with at least the same validity and reliability as the original instruments is expected to be obtained.
Effects of dimethylacetamide on chitosan/AgNP/GO fluid properties for 3D printing of water filtration membranes
Authors: Ogazi Anthony C. , Osifo Peter O.
Published: January 2023

This study aimed to prepare and characterize water‐soluble chitosan‐graphene oxide‐silver nanoparticles (CS‐GO‐AgNP) fluids for 3D‐inkjet printing of filtration membranes and to investigate the effects of Dimethylacetamide (DMAc) used as a co‐solvent on the rheological properties and printability of the modified chitosan fluids. DMAc concentration increase affected rheological characteristics of CS, resulting to a reduction in particle size distribution. The dynamic viscosity and shear stress of the ink reduced with increase in DMAc concentration, temperature and decrease in the mole fraction of chitosan. Surface tension of the fluid increased as the co‐solvent concentration increased, indicating a greater number of bond donor sites as a result of stronger hydrogen bond affinity of DMAc and increased molecular interactions with amide groups of CS. The optimal printability and drop formation of the modified CS ink were determined to be 63.8 mN/m (surface tension), 0.0105 Pas (viscosity), 1087 Kg/m3 (density), and a Z‐value of 6.1.
The generation mechanism of demolding force based on themold‐partinterface contact mode in micro‐injection molding
Authors: Zhou Jiawen , Qiu Zhongjun
Published: January 2023

Demolding is the key step of micro‐injection molding (μIM), which influences the molding quality of polymer parts to a great extent. The essence of demolding is to overcome interface interactions between the mold cavity surface and the part surface, which is closely related to factors such as the cavity surface topography and process parameters. However, a theoretical model predicting the demolding force of μIM is still lacking, resulting in the difficulty of improving the quality of demolding in μIM. Therefore, a comprehensive demolding force model is proposed to clarify the demolding mechanism of μIM. The model focuses on the adhesion behavior and friction behavior in the special contact mode formed by the replication effect of μIM. The theory proof and computation results indicate that the cavity surface topography determines the contact mode of the mold‐part interface (MPI), which in turn changes the real interface contact area, the composition mode of adhesion stress, and the friction forms, thereby affecting the adhesion and friction force during demolding. In addition, the process parameters can also change the contact mode of MPI as the process parameters have a great effect on the filling capacity and the degree of replication, thereby influencing the demolding process.
Proteoglycans in breast cancer, identification and characterization by LC‐MS/MS assisted proteomics approach: A review
Authors: Kizhakkeppurath Kumaran Ajeeshkumar , Sahu Ankita , Singh Astha , Aynikkattil Ravindran Nisha , Sekhar Chatterjee Niladri , Mathew Suseela , Verma Saurabh
Published: January 2023

Purpose

Proteoglycans (PGs) are negatively charged macromolecules containing a core protein and single or several glycosaminoglycan chains attached by covalent bond. They are distributed in all tissues, including extracellular matrix (ECM), cell surface, and basement membrane. They are involved in major pathways and cell signalling cascades which modulate several vital physiological functions of the body. They have also emerged as a target molecule for cancer treatment and as possible biomarkers for early cancer detection. Among cancers, breast cancer is a highly invasive and heterogenous type and has become the major cause of mortality especially among women. So, this review revisits the studies on PGs characterization in breast cancer using LC‐MS/MS‐based proteomics approach, which will be further helpful for identification of potential PGs‐based biomarkers or therapeutic targets.

Experimental design

There is a lack of comprehensive knowledge on the use of LC‐MS/MS‐based proteomics approaches to identify and characterize PGs in breast cancer.

Results

LC‐MS/MS assisted PGs characterization in breast cancer revealed the vital PGs in breast cancer invasion and progression. In addition, comprehensive profiling and characterization of PGs in breast cancer are efficiently carried out by this approach.

Conclusions

Proteomics techniques including LC‐MS/MS‐based identification of proteoglycans is effectively carried out in breast cancer research. Identification of expression at different stages of breast cancer is a major challenge, and LC‐MS/MS‐based profiling of PGs can boost novel strategies to treat breast cancer, which involve targeting PGs, and also aid early diagnosis using PGs as biomarkers.
Regulatory utility of physiologically based pharmacokinetic modeling for assessing food impact in bioequivalence studies: A workshop summary report
Authors: Al Shoyaib Abdullah , Riedmaier Arian Emami , Kumar Anita , Roy Partha , Parrott Neil John , Fang Lanyan , Tampal Nilufer , Yang Yuching , Jereb Rebeka , Zhao Liang , Wu Fang
Published: January 2023

This workshop report summarizes the presentations and panel discussion related to the use of physiologically based pharmacokinetic (PBPK) modeling approaches for food effect assessment, collected from Session 2 of Day 2 of the workshop titled “Regulatory Utility of Mechanistic Modeling to Support Alternative Bioequivalence Approaches.” The US Food and Drug Administration in collaboration with the Center for Research on Complex Generics organized this workshop where this particular session titled “Oral PBPK for Evaluating the Impact of Food on BE” presented successful cases of PBPK modeling approaches for food effect assessment. Recently, PBPK modeling has started to gain popularity among academia, industries, and regulatory agencies for its potential utility during bioavailability (BA) and/or bioequivalence (BE) studies of new and generic drug products to assess the impact of food on BA/BE. Considering the promises of PBPK modeling in generic drug development, the aim of this workshop session was to facilitate knowledge sharing among academia, industries, and regulatory agencies to understand the knowledge gap and guide the path forward. This report collects and summarizes the information presented and discussed during this session to disseminate the information into a broader audience for further advancement in this area.
Just say no to data listings!
Authors: Navarro Mercidita , Brucken Nancy , Yang Aiming , Ball Greg
Published: January 2023

Sponsor companies often create voluminous static listings for Clinical Study Reports (CSRs) and regulatory submissions, and possibly for internal use to review participant‐level data. This is likely due to the perception that they are required and/or lack of knowledge of various alternatives. However, there are other ways of viewing clinical study data that can provide an improved user experience, and are made possible by standard data structures such as the Study Data Tabulation Model (SDTM). The purpose of this paper is to explore some alternatives to providing a complete set of static listings and make a case for sponsors to begin considering these alternatives. We will discuss the recommendations from the PHUSE white paper, “Data Listings in Clinical Study Reports.”
Separation and characterization of the polymerized impurities in oxacillin sodium by 2D HPSEC and HPLC IT‐TOF MS
Authors: Gao Jiarui , Wang Fan , Zhang Xiangyu , Zhu Bingqi , Chen Xin , Li Ping , Zhou Ping , Zheng Jinqi , Wang Jian
Published: January 2023

Rationale

The polymerized impurities in oxacillin sodium can induce allergic reaction, which can seriously threaten the health of patients. Gel filtration chromatography (GFC) is currently widely used for the analysis of polymerized impurities, but it has drawbacks. To effectively control the polymerized impurities in oxacillin sodium, a high‐performance size exclusion chromatography (HPSEC) method and a reversed‐phase high performance liquid chromatography (RP‐HPLC) method were established to replace the classical GFC method.

Methods

By studying the chromatographic behavior of polymerized impurities and small molecular weight impurities in both methods with different chromatographic separation mechanisms, the polymerized impurities in oxacillin sodium were separated and detected effectively. Column‐switching two‐dimensional liquid chromatography was applied to eluted polymerized impurities from the HPSEC method for oxacillin sodium. Ion trap/time‐of‐flight mass spectrometry was applied to characterize the structures of polymerized impurities and unknown impurities eluted from the HPSEC/RP‐HPLC method for oxacillin sodium.

Results

The structures of 25 unknown impurities in oxacillin sodium were elucidated based on the high‐resolution massn data. Thirteen polymerized impurities were found and characterized. The corresponding relationship of impurities between the two methods was established and the specificity of the two methods was compared. The RP‐HPLC method for analysis of the polymerized impurities not only has higher column efficiency and more specificity than the HPSEC method, but also higher sensitivity.

Conclusions

The mechanisms of the formation of degradation impurities in oxacillin sodium were studied. The newly established RP‐HPLC methods could effectively separate and detect polymerized impurities and unknown impurities in oxacillin sodium. The study of the impurity profile in oxacillin sodium provided a scientific basis for the improvement of official monographs in pharmacopoeias.
Assisted reproductive technology in Japan: A summary report for 2020 by the ethics Committee of the Japan Society of obstetrics and gynecology
Authors: Katagiri Yukiko , Jwa Seung Chik , Kuwahara Akira , Iwasa Takeshi , Ono Masanori , Kato Keiichi , Kishi Hiroshi , Kuwabara Yoshimitsu , Harada Miyuki , Hamatani Toshio , Osuga Yutaka
Published: January 2023

Purpose

Since 1986, the Japan Society of Obstetrics and Gynecology assisted reproductive technology (ART) registry system has collected data on national ART use and outcomes trends in Japan. Herein, we describe the characteristics and outcomes of ART cycles registered during 2020 and compare the results with those from 2019.

Methods and Results

In 2020, 621 ART facilities participated in the registration. The total number of registered cycles was 449 900, and there were 60 381 live births, which decreased from the previous year (1.79% and 0.36% decrease, respectively). The number of freeze‐all in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles increased in 2020, and the number of neonates born was 2282 for IVF‐embryo transfer (ET) cycles and 2596 for ICSI cycles, which had decreased from the previous year. Frozen–thawed ET (FET) cycles had slightly increased from 2019 (0.04%). In 2020, 215 285 FET cycles were conducted, resulting in 76 196 pregnancies and 55 503 neonates. Single ET was performed in 81.6% of fresh transfers and 85.1% of frozen–thawed cycles, respectively, resulting in over 97% singleton pregnancies/livebirths rates.

Conclusion

Despite the COVID‐19 pandemic during 2020, the overall number of ART cycles and neonates born demonstrated only a slight decrease in 2020 compared with 2019.
Model selection with bootstrap validation
Authors: Savvides Rafael , Mäkelä Jarmo , Puolamäki Kai
Published: January 2023

Model selection is one of the most central tasks in supervised learning. Validation set methods are the standard way to accomplish this task: models are trained on training data, and the model with the smallest loss on the validation data is selected. However, it is generally not obvious how much validation data is required to make a reliable selection, which is essential when labeled data are scarce or expensive. We propose a bootstrap‐based algorithm, bootstrap validation (BSV), that uses the bootstrap to adjust the validation set size and to find the best‐performing model within a tolerance parameter specified by the user. We find that BSV works well in practice and can be used as a drop‐in replacement for validation set methods or k‐fold cross‐validation. The main advantage of BSV is that less validation data is typically needed, so more data can be used to train the model, resulting in better approximations and efficient use of validation data.
Robust deep neural network surrogate models with uncertainty quantification via adversarial training
Authors: Zhang Lixiang , Li Jia
Published: January 2023

Surrogate models have been used to emulate mathematical simulators of physical or biological processes for computational efficiency. High‐speed simulation is crucial for conducting uncertainty quantification (UQ) when the simulation must repeat over many randomly sampled input points (aka the Monte Carlo method). A simulator can be so computationally intensive that UQ is only feasible with a surrogate model. Recently, deep neural network (DNN) surrogate models have gained popularity for their state‐of‐the‐art emulation accuracy. However, it is well‐known that DNN is prone to severe errors when input data are perturbed in particular ways, the very phenomenon which has inspired great interest in adversarial training. In the case of surrogate models, the concern is less about a deliberate attack exploiting the vulnerability of a DNN but more of the high sensitivity of its accuracy to input directions, an issue largely ignored by researchers using emulation models. In this paper, we show the severity of this issue through empirical studies and hypothesis testing. Furthermore, we adopt methods in adversarial training to enhance the robustness of DNN surrogate models. Experiments demonstrate that our approaches significantly improve the robustness of the surrogate models without compromising emulation accuracy.
Prolinamide and Prolinamide Tagged with Ionic Liquid Intercalated in Bentonite Clay, a Recyclable Catalyst for Asymmetric Aldol Reactions
Authors: Deepa  , Singh Surendra
Published: January 2023

The imidazolium‐based chiral ionic liquids containing prolinamide moiety and prolinamide were intercalated in bentonite clay and evaluated in asymmetric aldol reactions of aromatic aldehydes or isatins with acetone or cyclohexanone. The 10 mol% of chiral ionic liquid having S‐phenylethylamine moiety 2 a catalyzed the direct enantioselective aldol reaction of isatins and acetone in i‐PrOH at −20 °C and afforded the corresponding 3‐alkyl‐3‐hydroxy indolin‐2‐ones in 72–98 % yields and 37–80 % ee's. The prolinamide intercalated in bentonite clay (0.125 g, 10 mol%) gave corresponding aldol products in 32–82 % yields and 38–91 % ee's. However, prolinamide intercalated bentonite clay was found to be less active as compared to chiral ionic liquids containing prolinamide. The prolinamide intercalated bentonite clay 8 was reused in four catalytic cycles, with a slight loss of activity and selectivity of the catalyst after the third recycling.