bluuebunny/crossref_metadata_2025 huggingface dataset:
The benefits and risks of pembrolizumab in combination with chemotherapy as first-line therapy in small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized control trials
Authors: Liu Qiangyun , Zhang Yixuan , Liu Miaowen , Xu Ruoxin , Yi Fengming , Wei Yiping , Zhu Shuqiang , Zhang Wenxiong
Published: October 2021

Background

Although pembrolizumab has shown clinical benefit in patients with small-cell lung cancer (SCLC), its actual efficacy in combination with a conventional chemotherapy drug has not been determined. We performed this study to discern the efficacy and risk of pembrolizumab in combination with chemotherapy as first-line therapy in SCLC patients.

Methods

We systematically searched the PubMed, ScienceDirect, Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar databases for relevant studies. The main outcomes were overall survival (OS) and progression-free survival (PFS).

Results

We identified 2980 articles and included 6 studies (5 were noncomparative open-label studies and 1 was a randomized controlled trial [RCT]) involving 396 patients in our meta-analysis. The pooled median OS (mOS) was 9.6 months (95% CI, 8.0-11.2), and the pooled median PFS (mPFS) was 4.2 months (95% CI, 2.2-6.1). The 1-year overall survival rate (OSR-1y) and 6-month progression-free survival rate (PFSR-6m) were 45.1% (95% CI, 33-57.2%) and 41.6% (95% CI, 24.3-59%), respectively. The objective response rate (ORR) was 38.8% (95% CI, 11.9-65.67%), disease control rate (DCR) was 69.30% (95% CI, 51.6-87.0%), complete response (CR) was 2.20% (95% CI, 0.8-3.7%), partial response (PR) was 34.70% (95% CI, 7.8-61.5%), and stable disease (SD) was 20.90% (95% CI, 9.1-32.6%). The grade 3-4 adverse effect (AE) rate was 20.88% (95% CI, 1.22-54.85%). The most common AEs were neutropenia (90.16%), anemia (53.21%), dysphagia (41.96%), platelet count decrease (34.87%), and esophagitis (32.89%); severe AEs included neutropenia, respiratory failure, pneumonitis, acute coronary syndrome, and colitis/intestinal ischemia.

Conclusions

The combination of pembrolizumab with conventional chemotherapy is an effective therapeutic schedule with acceptable and manageable efficacy and toxicity in patients with SCLC. More high-quality and well-designed RCTs with large sample sizes are warranted to further validate our findings.
Generating synthetic CT from low-dose cone-beam CT by using generative adversarial networks for adaptive radiotherapy
Authors: Gao Liugang , Xie Kai , Wu Xiaojin , Lu Zhengda , Li Chunying , Sun Jiawei , Lin Tao , Sui Jianfeng , Ni Xinye
Published: October 2021

Objective

To develop high-quality synthetic CT (sCT) generation method from low-dose cone-beam CT (CBCT) images by using attention-guided generative adversarial networks (AGGAN) and apply these images to dose calculations in radiotherapy.

Methods

The CBCT/planning CT images of 170 patients undergoing thoracic radiotherapy were used for training and testing. The CBCT images were scanned under a fast protocol with 50% less clinical projection frames compared with standard chest M20 protocol. Training with aligned paired images was performed using conditional adversarial networks (so-called pix2pix), and training with unpaired images was carried out with cycle-consistent adversarial networks (cycleGAN) and AGGAN, through which sCT images were generated. The image quality and Hounsfield unit (HU) value of the sCT images generated by the three neural networks were compared. The treatment plan was designed on CT and copied to sCT images to calculated dose distribution.

Results

The image quality of sCT images by all the three methods are significantly improved compared with original CBCT images. The AGGAN achieves the best image quality in the testing patients with the smallest mean absolute error (MAE, 43.5 ± 6.69), largest structural similarity (SSIM, 93.7 ± 3.88) and peak signal-to-noise ratio (PSNR, 29.5 ± 2.36). The sCT images generated by all the three methods showed superior dose calculation accuracy with higher gamma passing rates compared with original CBCT image. The AGGAN offered the highest gamma passing rates (91.4 ± 3.26) under the strictest criteria of 1 mm/1% compared with other methods. In the phantom study, the sCT images generated by AGGAN demonstrated the best image quality and the highest dose calculation accuracy.

Conclusions

High-quality sCT images were generated from low-dose thoracic CBCT images by using the proposed AGGAN through unpaired CBCT and CT images. The dose distribution could be calculated accurately based on sCT images in radiotherapy.
The combined effect of vitamin K and calcium on bone mineral density in humans: a meta-analysis of randomized controlled trials
Authors: Hu Liyou , Ji Jindou , Li Dong , Meng Jing , Yu Bo
Published: October 2021

Background

With the increasing incidence of osteoporosis, vitamin K and calcium have been linked to bone mineral density (BMD) and undercarboxylated osteocalcin (UcOC) in many studies, but the results of studies of the combined effect of vitamin K and calcium on BMD and UcOC in humans have been inconsistent. We conducted a systematic review of randomized controlled trials to assess the effect of this combination treatment on BMD and UcOC in humans.

Methods

A search for articles was conducted using PubMed, Embase, and the Cochrane Library database up to March 2021 (no language restrictions). We also reviewed the reference lists of the relevant publications and reviews to locate additional publications. The standard mean difference (SMD) was used as the primary measure of effect size. Our main endpoints were lumbar BMD, femoral neck BMD, hip BMD, total femoral BMD, and UcOC from baseline to end point. We performed subgroup analysis, heterogeneity testing, and assessment of publication bias.

Results

A total of 1346 patients from 10 randomized controlled trials were included in the meta-analysis. The forest plot analysis revealed that vitamin K combined with calcium was associated with a higher lumbar spine BMD compared to controls. The SMD was 0.20 [95% confidence interval (CI): 0.07 to 0.32]. Vitamin K and calcium supplementation led to a significant decrease in UcOC (SMD: − 1.71, 95% CI: − 2.45 to − 0.96). Subgroup analysis showed that vitamin K2 and vitamin K1 had SMDs of 0.30 (95% CI: 0.10 to 0.51) and SMDs of 0.14 (95% CI: − 0.02 to 0.29), and calcium dosages of ≤ 1000 mg/d or > 1000 mg/d had SMDs of 0.19 (95% CI: 0.05 to 0.32) and 0.26 (95% CI: − 0.04 to 0.55).

Conclusion

The combination of vitamin K and calcium has a positive effect on lumbar BMD and decreases the level of UcOC.

Registration: The protocol for this meta-analysis was registered at the International Prospective Register of Systematic Reviews (CRD42021251825).
Evaluation of the feasibility of acetabular cup pre-determination in revision total hip arthroplasty via X-ray of the bone stock of the anterosuperior acetabulum
Authors: Zhang Jingwei , Kong Keyu , Chi Yingjun , Liu Xiaoliang , Zeng Yiming , Li Huiwu
Published: October 2021

Purpose

This study was aimed to explore (1) location on AP pelvic X-ray that displayed bone stock in anterosuperior acetabulum; (2) whether X-ray could provide enough evidence to evaluate whether bone stock could provide support for acetabular cup; (3) criteria to determine whether anterosuperior bone stock could provide sufficient support for cup on X-ray.

Methods

Our study retrospectively collected 43 patients who underwent revision THA for cup loosening from 2014 to 2019. The position of anterosuperior acetabular bone stock was compared between X-ray and CT-based 3-D reconstruction. Seventy-millimeter acetabular cup was implanted simulatively to obtain the contact line between acetabular cup and superolateral remaining bone stock. The contact line length and the angle were measured. Patients were divided into cup group and cage group, and ROC curves of both contact line length and angle were drawn.

Results

The superolateral part of acetabulum on X-ray could reflect the anterosuperior host bone stock of acetabulum according to the comparison of anteroposterior pelvic X-ray and 3-D reconstruction. Critical point was chosen when we got the highest sensitivity with a 100% specificity in ROC curves. The critical values of contact length and angle were 15.58 mm and 25.5°.

Conclusions

Surgeons could assess the anterosuperior bone stock of acetabulum by AP pelvic X-ray to decide whether revision could be done merely using cup or need customized cage. Clinically, when contact line length was larger than 16 mm or contact angle was larger than 25.5°, adoption of cup could obtain primary stability in the revision surgery in most cases.
The risk for complications and reoperations with the use of mega prostheses in bone reconstructions
Authors: Berger Christina , Larsson Sofia , Bergh Peter , Brisby Helena , Wennergren David
Published: October 2021

Background

Despite a relatively high risk for complications and reoperations, mega prostheses are considered a useful method for reconstruction of bone defects after tumour resections. The total number of reoperations has not previously been described, and little is known about the complication rate of mega prostheses used for other indications than primary bone tumours.

Questions/purposes

The current retrospective observational study aimed to describe the patient population treated with mega prostheses at Sahlgrenska University Hospital, Sweden, during 14 consecutive years, reports the complications leading to reoperation and the number and type of reoperations for different kinds of complications, and reports on implant survival.

Methods

All patients treated with a mega prosthesis, regardless of surgical indication and anatomical location, at Sahlgrenska University Hospital during the period 2006–2019 were identified. The medical records for all patients were reviewed. Data regarding age, sex, diagnosis, site of disease, bone resection length, chemotherapeutical treatment and postoperative complications including infections and oncological outcome, were collected and evaluated.

Results

One hundred and fourteen patients treated with 116 mega prostheses were included in the study. The predominant indication for primary surgery with a mega prosthesis was sarcoma of either bone or soft tissue (53.5% of the patients). In total 51 prostheses (44%) did not require any reoperation after the primary surgery. The most common reason for reoperation was infection (22%) followed by soft tissue failure (13%). The risk for prosthetic infection was significantly higher in the group of patients operated due to sarcoma compared with all other indications for surgery regardless of surgical site (p = 0.004).

Conclusion

The study reveals a total reoperation rate of 56% after reconstructive surgery using mega prostheses. Despite the high reoperation rates, at the end of the study period, 83% of the patients had still a functioning prosthesis. Therefore, the use of mega prostheses can be considered a reliable method for reconstruction of large bone defects in selected patients.

Level of Evidence

Level IV, therapeutic study.
Investigation of anti-osteoporosis mechanisms of Rehmanniae Radix Preparata based on network pharmacology and experimental verification
Authors: Ou Li , Kang Wenqian , Liang Ziyi , Gao Feng , Dong Taiwei , Wei Peifeng , Li Min
Published: October 2021

Background

Rehmanniae Radix Preparata (RRP) can effectively improve the symptoms of osteoporosis, but its molecular mechanism for treating osteoporosis is still unclear. The objective of this study is to investigate the anti-osteoporosis mechanisms of RRP through network pharmacology.

Methods

The overlapping targets of RRP and osteoporosis were screened out using online platforms. A visual network diagram of PPI was constructed and analyzed by Cytoscape 3.7.2 software. Molecular docking was used to evaluate the binding activity of ligands and receptors, and some key genes were verified through pharmacological experiments.

Results

According to topological analysis results, AKT1, MAPK1, ESR1, and SRC are critical genes for RRP to treat osteoporosis, and they have high binding activity with stigmasterol and sitosterol. The main signal pathways of RRP in the treatment of osteoporosis, including the estrogen signaling pathway, HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway. Results of animal experiments showed that RRP could significantly increase the expression levels of Akt1, MAPK1, ESR1, and SRC1 mRNA in bone tissue to increase bone density.

Conclusion

This study explained the coordination between multiple components and multiple targets of RRP in the treatment of osteoporosis and provided new ideas for its clinical application and experimental research.
Circ_0061140 knockdown inhibits tumorigenesis and improves PTX sensitivity by regulating miR-136/CBX2 axis in ovarian cancer
Authors: Zhu Jun , Luo Jun-e , Chen Yurong , Wu Qiong
Published: October 2021

Background

Ovarian cancer is an aggressive tumor in women with high mortality. Paclitaxel (PTX) can be used for the chemotherapy of ovarian cancer. Here, the roles of circular_0061140 (circ_0061140) in PTX sensitivity and malignant progression of ovarian cancer are unveiled.

Methods

The expressions of circ_0061140, microRNA-136 (miR-136) and chromobox 2 (CBX2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was determined by western blot. The half maximal inhibitory concentration (IC50) of PTX was determined by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation was investigated by cell counting kit-8 (CCK-8) and colony formation assays. Cell apoptosis was demonstrated by flow cytometry analysis. Cell migration and invasion were evaluated by transwell assay. The binding relationship between miR-136 and circ_0061140 or CBX2 was predicted by interactome or starbase online database, and identified by dual-luciferase reporter assay. The effects of circ_0061140 on tumor formation and PTX sensitivity in vivo were disclosed by tumor formation assay.

Results

Circ_0061140 and CBX2 expressions were upregulated, while miR-136 expression was downregulated in PTX-resistant tissues and cells compared with control groups. Circ_0061140 knockdown repressed cell proliferation, migration and invasion, and promoted cell apoptosis and PTX sensitivity; however, these effects were restrained by miR-136 RNAi. Additionally, circ_0061140 was a sponge of miR-136, and miR-136 bound to CBX2. Furthermore, circ_0061140 knockdown inhibited tumor formation and improved PTX sensitivity in vivo.

Conclusions

Circ_0061140 silencing repressed the progression and PTX resistance of ovarian cancer by downregulating CBX2 expression via sponging miR-136, which provided novel insight into studying the therapy of ovarian cancer with PTX.
Efficacy of electroacupuncture in patients with failed back surgery syndrome: study protocol for a randomized controlled trial
Authors: Sheng Xiaoping , Yue Hongyu , Zhang Qi , Chen Deta , Qiu Weidong , Tang Jun , Fan Tianyou , Gu Jingliang , Jiang Bingchen , Qiu Minlei , Chen Lin
Published: October 2021

Background

Persistent pain following back surgery called failed back surgery syndrome remains a major treatment challenge. The aim of this study is to evaluate the efficacy and safety of electroacupuncture on relieving back pain in FBSS patients.

Methods/design

This is a randomized, single-blind, single-site, placebo-controlled trial. A total of 144 eligible FBSS patients will be randomly assigned to the electroacupuncture, manual acupuncture, or sham acupuncture group in a 1:1:1 ratio. Each group will receive 2 treatment sessions per week for 12 weeks. The primary outcome will be low back pain intensity based on the 11-point numerical rating scale (NRS). The secondary outcomes include Oswestry Disability Index (ODI) questionnaire, Beck Depression Inventory-II (BDI-II), Pittsburgh Sleep Quality Index (PSQI), and analgesic consumption. All clinical outcomes will be collected at baseline, during the treatment phase (at 8 and 12 weeks), and at the 16-, 24- and 36-week follow-ups. All data will be analyzed based on the intention-to-treat principle and adverse events will be assessed during the trial.

Discussion

This pilot randomized controlled trial will evaluate the efficacy of electroacupuncture for treating failed back surgery syndrome. The outcomes will determine whether electroacupuncture is efficacious in relieving low back pain as well as improving the quality of life in failed back surgery syndrome patients.

Trial registration

Chinese Clinical Trial Registry ChiCTR2000040144. Registered on 22 November 2020
Changes in porcine nutrient transport physiology in response to Ascaris suum infection
Authors: Koehler Sarina , Springer Andrea , Issel Nicole , Klinger Stefanie , Strube Christina , Breves Gerhard
Published: October 2021

Background

The roundworm Ascaris suum is one of the parasites with the greatest economic impact on pig farming. In this context, lower weight gain is hypothesized to be due to decreased nutrient absorption. This study aims at characterizing the effects of A. suum infection on intestinal nutrient transport processes and potential molecular mechanisms.

Methods

Three groups of six piglets each were infected orally (10,000 embryonated A. suum eggs) in a single dose (“single infection”). Another three groups were infected orally (1000 embryonated eggs) for 10 consecutive days (“trickle infection”). Animals were necropsied 21, 35 and 49 days post-infection (dpi). Three groups served as respective controls. The Ussing chamber technique was applied for the functional characterization of small intestinal tissues [short-circuit currents (Isc) as induced by glucose, alanine and peptides; 3H-glucose net flux rates; tissue conductance (Gt)]. Transcription and expression levels of relevant cytokines and nutrient transporters were evaluated (qPCR/western blot).

Results

Peptide- and alanine-induced changes in Isc were significantly decreased in the jejunum and ileum of the trickle-infected group at 49 dpi and in the ileum of the single-infected group at 49 dpi. No significant differences regarding glucose transport were observed between the Ascaris-infected groups and the control group in Ussing chamber experiments. Transcription levels of the glucose and peptide transporters as well as of selected transcription factors (transcription of signal transducer and activator of transcription 6 [STAT6] and hypoxia-inducible factor 1-alpha [Hif-1α]) were significantly increased in response to both infection types after some periods. The transcription of interleukins 4 and 13 varied between decrease and increase regarding the respective time points, as did the protein expression of glucose transporters. The expression of the peptide transporter PepT1 was significantly decreased in the ileal single-infected group at 35 dpi. Hif-1α was significantly increased in the ileal tissue from the single-infected group at 21 dpi and in the trickle-infected group at 35 dpi. The expression levels of Na+/K+-ATPase and ASCT1 remained unaffected.

Conclusions

In contrast to the current hypothesis, these results indicate that the nutrient deprivation induced by A. suum cannot be explained by transcriptional or expression changes alone and requires further studies.

Graphical abstract
Red foxes harbor two genetically distinct, spatially separated Echinococcus multilocularis clusters in Brandenburg, Germany
Authors: Herzig Mandy , Maksimov Pavlo , Staubach Christoph , Romig Thomas , Knapp Jenny , Gottstein Bruno , Conraths Franz J.
Published: October 2021

Background

Alveolar echinococcosis (AE) is a clinically serious zoonosis caused by the fox tapeworm Echinococcus multilocularis. We studied the diversity and the distribution of genotypes of E. multilocularis isolated from foxes in Brandenburg, Germany, and in comparison to a hunting ground in North Rhine-Westphalia.

Methods

Echinococcus multilocularis specimens from 101 foxes, 91 derived from Brandenburg and 10 derived from North Rhine-Westphalia, were examined. To detect potential mixed infections with different genotypes of E. multilocularis, five worms per fox were analyzed. For genotyping, three mitochondrial markers, namely cytochrome c oxidase subunit 1 (Cox1), NADH dehydrogenase subunit 1 (Nad1), and ATP synthase subunit 6 (ATP6), and the nuclear microsatellite marker EmsB were used. To identify nucleotide polymorphisms, the mitochondrial markers were sequenced and the data were compared, including with published sequences from other regions. EmsB fragment length profiles were determined and confirmed by Kohonen network analysis and grouping of Sammon’s nonlinear mapping with k-means clustering. The spatial distribution of genotypes was analyzed by SaTScan for the EmsB profiles found in Brandenburg.

Results

With both the mitochondrial makers and the EmsB microsatellite fragment length profile analyses, mixed infections with different E. multilocularis genotypes were detected in foxes from Brandenburg and North Rhine-Westphalia. Genotyping using the mitochondrial markers showed that the examined parasite specimens belong to the European haplotype of E. multilocularis, but a detailed spatial analysis was not possible due to the limited heterogeneity of these markers in the parasite population. Four (D, E, G, and H) out of the five EmsB profiles described in Europe so far were detected in the samples from Brandenburg and North Rhine-Westphalia. The EmsB profile G was the most common. A spatial cluster of the E. multilocularis genotype with the EmsB profile G was found in northeastern Brandenburg, and a cluster of profile D was found in southern parts of this state.

Conclusions

Genotyping of E. multilocularis showed that individual foxes may harbor different genotypes of the parasite. EmsB profiles allowed the identification of spatial clusters, which may help in understanding the distribution and spread of the infection in wildlife, and in relatively small endemic areas.

Graphical Abstract
The principal eigenvalue of some nth order linear boundary value problems
Authors: Almenar Pedro , Jódar Lucas
Published: October 2021

The purpose of this paper is to present a procedure for the estimation of the smallest eigenvalues and their associated eigenfunctions of nth order linear boundary value problems with homogeneous boundary conditions defined in terms of quasi-derivatives. The procedure is based on the iterative application of the equivalent integral operator to functions of a cone and the calculation of the Collatz–Wielandt numbers of such functions. Some results on the sign of the Green functions of the boundary value problems are also provided.
Microbial colonization and resistome dynamics in food processing environments of a newly opened pork cutting industry during 1.5 years of activity
Authors: Cobo-Díaz José F. , Alvarez-Molina Adrián , Alexa Elena A. , Walsh Calum J. , Mencía-Ares Oscar , Puente-Gómez Paula , Likotrafiti Eleni , Fernández-Gómez Paula , Prieto Bernardo , Crispie Fiona , Ruiz Lorena , González-Raurich Montserrat , López Mercedes , Prieto Miguel , Cotter Paul , Alvarez-Ordóñez Avelino
Published: October 2021

Background

The microorganisms that inhabit food processing environments (FPE) can strongly influence the associated food quality and safety. In particular, the possibility that FPE may act as a reservoir of antibiotic-resistant microorganisms, and a hotspot for the transmission of antibiotic resistance genes (ARGs) is a concern in meat processing plants. Here, we monitor microbial succession and resistome dynamics relating to FPE through a detailed analysis of a newly opened pork cutting plant over 1.5 years of activity.

Results

We identified a relatively restricted principal microbiota dominated byPseudomonasduring the first 2 months, while a higher taxonomic diversity, an increased representation of other taxa (e.g.,Acinetobacter,Psychrobacter), and a certain degree of microbiome specialization on different surfaces was recorded later on. An increase in total abundance, alpha diversity, and β-dispersion of ARGs, which were predominantly assigned toAcinetobacterand associated with resistance to certain antimicrobials frequently used on pig farms of the region, was detected over time. Moreover, a sharp increase in the occurrence of extended-spectrum β-lactamase-producingEnterobacteriaceaeand vancomycin-resistantEnterococcaceaewas observed when cutting activities started. ARGs associated with resistance to β-lactams, tetracyclines, aminoglycosides, and sulphonamides frequently co-occurred, and mobile genetic elements (i.e., plasmids, integrons) and lateral gene transfer events were mainly detected at the later sampling times in drains.

Conclusions

The observations made suggest that pig carcasses were a source of resistant bacteria that then colonized FPE and that drains, together with some food-contact surfaces, such as equipment and table surfaces, represented a reservoir for the spread of ARGs in the meat processing facility.
3-Bromopyruvate-mediated MCT1-dependent metabolic perturbation sensitizes triple negative breast cancer cells to ionizing radiation
Authors: Skaripa-Koukelli Irini , Hauton David , Walsby-Tickle John , Thomas Eloïse , Owen Joshua , Lakshminarayanan Abirami , Able Sarah , McCullagh James , Carlisle Robert C. , Vallis Katherine A.
Published: October 2021

Background

Triple negative breast cancer (TNBC) poses a serious clinical challenge as it is an aggressive form of the disease that lacks estrogen receptor, progesterone receptor, and ERBB2 (formerly HER2) gene amplification, which limits the treatment options. The Warburg phenotype of upregulated glycolysis in the presence of oxygen has been shown to be prevalent in TNBC. Elevated glycolysis satisfies the energy requirements of cancer cells, contributes to resistance to treatment by maintaining redox homeostasis and generating nucleotide precursors required for cell proliferation and DNA repair. Expression of the monocarboxylate transporter 1 (MCT1), which is responsible for the bidirectional transport of lactate, correlates with an aggressive phenotype and poor outcome in several cancer types, including breast cancer. In this study, 3-bromopyruvate (3BP), a lactate/pyruvate analog, was used to selectively target TNBC cells that express MCT1.

Methods

The cytotoxicity of 3BP was tested in MTT assays using human TNBC cell lines: BT20 (MCT1+/MCT4−), MDA-MB-23 (MCT1−/MCT4+), and BT20 in which MCT1 was knocked down (siMCT1-BT20). The metabolite profile of 3BP-treated and 3BP-untreated cells was investigated using LC-MS/MS. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of BT20 and MDA-MB-231 cells treated with 3BP were measured using a Seahorse XF96 extracellular flux analyzer. The impact of ionizing radiation on cell survival, alone or in combination with 3BP pre-treatment, was evaluated using clonogenic assays.

Results

Metabolomic analyses showed that 3BP causes inhibition of glycolysis, disturbance of redox homeostasis, decreased nucleotide synthesis, and was accompanied by a reduction in medium acidification. In addition, 3BP potentiated the cytotoxic effect of ionizing radiation, a treatment that is frequently used in the management of TNBC.

Conclusions

Overall, MCT1-mediated metabolic perturbation in combination with radiotherapy is shown to be a promising strategy for the treatment of glycolytic tumors such as TNBC, overcoming the selectivity challenges of targeting glycolysis with glucose analogs.
Qualitative patient experiences from the Self-Blame and Perspective-Taking Intervention for eating disorders
Authors: Hagan Whitney Smith , Mericle Susan , Hunt Bethany J. , Harper Jessica A. , Palka Jayme M. , Pelfrey Sarah , McAdams Carrie J.
Published: October 2021

Background

Problems in social cognition and social support contribute to eating disorders (ED). Group therapy provides an ideal format to create an experiential learning environment focused on understanding social interactions. This pilot study examined the qualitative content of the participants’ experiences in the Self-Blame and Perspective-Taking Intervention (SBPI) for ED.

Methods

The SBPI was a 4-week group therapy intervention involving art therapy and psychoeducation that focused on social behaviors in ED patients. Participants received surveys immediately after the intervention and at 1 to 4 weeks after the post-intervention. Thematic analyses of qualitative feedback were performed using Braun and Clarke’s thematic analysis framework.

Results

Inductive analyses revealed three main themes: (1) Developing self-acceptance through emotional reflection, (2) Changing expectations with neurosocial knowledge, and (3) Bonding and vulnerability in social interactions; all concepts intentionally targeted by the SBPI. Participants varied in their support of a guideline to exclude personal discussion of ED-related cognitions and behaviors in the group.

Conclusions

As a whole, patients valued the combination of psychosocial education with group experientials focused on social behavior. Positive feedback from the SBPI suggests that adjunctive treatments that target mental-wellness constructs indirectly related to ED pathology may be helpful by allowing patients to see themselves as separable from the illness.

Trial registrationClinicalTrials.gov, NCT0487758. Registered 7 May 2021—Retrospectively registered.https://clinicaltrials.gov/ct2/show/NCT04877158.
A pioneer of acrylic painting: new insights into Carmen Herrera’s studio practice
Authors: Pozzi Federica , Basso Elena , Centeno Silvia A. , Duvernois Isabelle , Arslanoglu Julie
Published: October 2021

Carmen Herrera, born on May 30th, 1915, is a Cuban American abstract minimalist artist, whose first solo show was held at the Whitney Museum of American Art, New York, in 2016–2017. On this occasion, a scientific study of five paintings from the artist’s time in Paris (1948–1953) revealed her pioneering use of solvent-based acrylic paints in post-war Europe. This article presents a second phase of research into Herrera’s work aiming to shed light on her studio practice and ascertain the possible presence of other early acrylic paints in her pre-1963 artistic production. A selection of four paintings, namely Iberia #25 (1948), Iberic (1949), Flights of Colors #16 (1949), and Early Dynasty (1953), was subjected to an analytical campaign that relied on both non-invasive and micro-invasive techniques. Results confirmed the use of both oil and solvent-based acrylic paints, supporting our primary research and uncovering the first-known occurrence of acrylic binders in Herrera’s Iberia #25. In all cases, the ground layer consists of a mixture of titanium white in its tetragonal form of rutile, anhydrite, and talc, while the color palette was found to be based on both traditional and modern pigments. In most areas, several paint layers appeared to be overlaid on top of one another, revealing a creative process that developed through subsequent compositions. Remnants of earlier paint layers, which appeared to have been scraped off before new ones were applied, were observed directly above the ground in some of the samples examined. In addition, Iberia #25 and Iberic, with analogous geometric and chromatic schemes, underwent technical imaging, which exposed pencil lines and notes underneath the paint layers likely indicative of the intended design and polychromy. Besides corroborating a major alteration in the current scholarship on the availability and use of acrylic-based artists’ paints in post-war Europe, this research provides new insights into Herrera’s materials, techniques, and studio practice. In addition, the results of this scientific study assisted the development of a suitable treatment plan for Iberic in preparation for its display in The Metropolitan Museum of Art’s galleries as part of the museum’s 150th anniversary exhibition Making The Met, 1870–2020.
Peritonsillar infiltration of lidocaine Hcl versus intravenous pre-incisional lornoxicam in reducing post-tonsillectomy pain: this is a prospective, randomized, double-blinded, placebo-controlled study
Authors: Zittoon Reham Farouk , Hassan Eman Youssef , Ibrahem Ibrahem Hassan , Baher Maged Mohamed
Published: October 2021

Background

Tonsillectomy is one of the most common procedures in otorhinolaryngology practice where analgesics are required for pain-relief especially in children. To compare the efficacy of using peritonsillar infiltration of lidocaine Hcl versus intravenous preincisional lornoxicam in reducing post tonsillectomy pain.

Results

Prospective, randomized, double-blinded, placebo-controlled study. Ninety-nine patients from age 12 to 18 years old, prepared for tonsillectomy. Patients were randomly subdivided into three groups as 33 patient in each group to receive either lidocaine (group 1), lornoxicam (group 2), or saline as a placebo (group 3). Anesthesia was induced using intravenous fentanyl and propofol, while endotracheal intubation was facilitated with rocuronium and maintenance by halothan. Intraoperative bleeding, pain scores, interval until first order for analgesic. The postoperative complications including bleeding, hypoxia, nausea, and vomiting also were observed. Pain scores at rest were significantly lower in group 2 than groups 1 and 3 at all observation times. Similarly, pain scores were lower in group 2 during the first 5 postoperative hours. The mean time for rescue analgesic was 276 min in group 2, 91 min in group 1, and about 60 min in group 3. No significant differences were noted for intraoperative bleeding.

Conclusion

The use of lornoxicam 16 mg at preoperative phase gave good control of immediate post tonsillectomy pain.

Level of evidence

3b
Up-Front Multigene Panel Testing for Cancer Susceptibility in Patients With Newly Diagnosed Endometrial Cancer: A Multicenter Prospective Study
Authors: Levine Monica D. , Pearlman Rachel , Hampel Heather , Cosgrove Casey , Cohn David , Chassen Alexis , Suarez Adrian , Barrington David A. , McElroy Joseph P. , Waggoner Steven , Nakayama John , Billingsley Caroline , Resnick Kim , Andrews Stephen , Singh Sareena , Jenison Eric , Clements Aine , Neff Robert , Goodfellow Paul J. ,   for the Ohio Prevention and Treatment of Endometrial Cancer Initiative Study Group
Published: October 2021

PURPOSE

Clinical utility of up-front multigene panel testing (MGPT) is directly related to the frequency of pathogenic variants (PVs) in the population screened and how genetic findings can be used to guide treatment decision making and cancer prevention efforts. The benefit of MGPT for many common malignancies remains to be determined. In this study, we evaluated up-front MGPT in unselected patients with endometrial cancer (EC) to determine the frequency of PVs in cancer susceptibility genes.

METHODS

Patients with EC were prospectively enrolled at nine Ohio institutions from October 1, 2017, to December 31, 2020. Nine hundred and sixty-one patients with newly diagnosed EC underwent clinical germline MGPT for 47 cancer susceptibility genes. In addition to estimating the prevalence of germline PVs, the number of individuals identified with Lynch syndrome (LS) was compared between MGPT and tumor-based screening.

RESULTS

Likely pathogenic variants or PVs were identified in 97 of 961 women (10.1%). LS was diagnosed in 29 of 961 patients (3%; 95% CI, 2.1 to 4.3), with PVs in PMS2 most frequent. MGPT revealed nine patients with LS in addition to the 20 identified through routine tumor-based screening. BRCA1 and BRCA2 PVs were found in 1% (10 of 961; 95% CI, 0.6 to 1.9) of patients and that group was significantly enriched for type II ECs.

CONCLUSION

This prospective, multicenter study revealed potentially actionable germline variants in 10% of unselected women with newly diagnosed EC, supporting the use of up-front MGPT for all EC patients. The discovery that BRCA1 or BRCA2 heterozygotes frequently had type II cancers points to therapeutic opportunities for women with aggressive histologic EC subtypes.
Time-Resolved EPR and Theoretical Investigations of Naphthalene Diimide Spin Dynamics in the Excited State
Authors: Matsuoka Hideto , Shibano Yuki , Akimoto Ikuko , Kanzaki Yuki
Published: October 2021

Naphthalene diimides (NDIs) are a promising material for n-type polymer acceptors in thin-film devices such as organic light-emitting diodes. The intersystem crossing (ISC) pathway of NDIs has been extensively studied, relying heavily on the accuracy of quantum chemical calculations. However, the theoretical results are inconsistent with the experimental findings. In this work, time-resolved electron paramagnetic resonance (tr-EPR) was applied to NDIs for the first time in order to elucidate the ISC pathway and assign their electronic structures. With the help of quantum chemical calculations, tr-EPR clearly demonstrated that ISC occurs via an upper excited triplet state (T4) after photoexcitation. The zero-field splitting (ZFS) constants of the NDIs, which strongly correlate with their spin density distributions, were experimentally determined by tr-EPR. We demonstrate that an ab initio complete active space self-consistent field is required to interpret the ZFS constants of the NDIs. From the theoretical analyses of the constants and phosphorescence measurements, the spin state observed in the tr-EPR spectra was identified as the lowest excited triplet state, illustrating that quick internal conversion occurs after the ISC process.
Cost-effectiveness of patient navigation for lung cancer – a systematic review
Authors: Kass Benjamin , Dornquast Christina , Rieckmann Nina , Goerling Ute , Holmberg Christine , Reinhold Thomas
Published: October 2021

Background: Patient navigation (PN) programs have been shown to increase patient satisfaction and quality of life among patients with lung cancer and to decrease time to treatment. However, the general cost-effectiveness of such programs in the context of lung cancer remains unknown. Hence, the aim of the present systematic review was to analyze the scientific literature and quantitatively assess the level of evidence on the cost-effectiveness of PN programs for patients diagnosed with lung cancer. 

Methods: A systematic literature search was carried out in PubMed, EMBASE, CENTRAL, CINAHL and PsycINFO databases without time limitations. Randomized controlled trials written in English or German were eligible for inclusion if any results regarding the cost-effectiveness of personally delivered PN programs for patients after lung cancer diagnosis were reported. A manual search was carried out to supplement the systematic search. Additionally, the authors of ongoing or unpublished relevant research were contacted. The titles, abstracts and full texts of relevant citations were screened independently by two reviewers.  

Results: The initial search yielded 814 articles, including four papers identified manually. Twenty-one articles were included in the full text screening. However, no study met the inclusion criteria. Contacting the authors of ongoing or unpublished research and cross-cancer studies did not yield any studies that met the inclusion criteria.  

Conclusion: Since no study met the inclusion criteria, this study reveals a research gap in this area. Furthermore, no conclusive statement regarding the cost-effectiveness of patient navigation programs for patients diagnosed with lung cancer can be made. Since the implementation of new healthcare models such as PN at least partially depends on their cost-effectiveness, future attempts to evaluate PN programs for lung cancer patients should consider examining outcomes related to cost-effectiveness to overcome the identified research gap.
Toxin-like peptides in plasma, urine and faecal samples from COVID-19 patients
Authors: Brogna Carlo , Cristoni Simone , Petrillo Mauro , Querci Maddalena , Piazza Ornella , Van den Eede Guy
Published: October 2021

Background: SARS-CoV-2 that causes COVID-19 disease and led to the pandemic currently affecting the world has been broadly investigated. Different studies have been performed to understand the infection mechanism, and the involved human genes, transcripts and proteins. In parallel, numerous clinical extra-pulmonary manifestations co-occurring with COVID-19 disease have been reported and evidence of their severity and persistence is increasing. Whether these manifestations are linked to other disorders co-occurring with SARS-CoV-2 infection, is under discussion. In this work, we report the identification of toxin-like peptides in COVID-19 patients by application of the Liquid Chromatography Surface-Activated Chemical Ionization – Cloud Ion Mobility Mass Spectrometry.  

Methods: Plasma, urine and faecal samples from COVID-19 patients and control individuals were analysed to study peptidomic toxins’ profiles. Protein precipitation preparation procedure was used for plasma, to remove high molecular weight proteins and efficiently solubilize the peptide fraction; in the case of faeces and urine, direct peptide solubilization was employed.  

Results: Toxin-like peptides, almost identical to toxic components of venoms from animals, like conotoxins, phospholipases, phosphodiesterases, zinc metal proteinases, and bradykinins, were identified in samples from COVID-19 patients, but not in control samples. 

Conclusions: The presence of toxin-like peptides could potentially be connected to SARS-CoV-2 infection. Their presence suggests a possible association between COVID-19 disease and the release in the body of (oligo-)peptides almost identical to toxic components of venoms from animals. Their involvement in a large set of heterogeneous extra-pulmonary COVID-19 clinical manifestations, like neurological ones, cannot be excluded. Although the presence of each individual symptom is not selective of the disease, their combination might be related to COVID-19 by the coexistence of the panel of the here detected toxin-like peptides. The presence of these peptides opens new scenarios on the aetiology of the COVID-19 clinical symptoms observed up to now, including neurological manifestations.
“The Trout Breaks the Ice” by Mikhail Kuzmin: Verse and Grammar
Authors: Akimova Marina
Published: October 2021

The author explores various compositional levels of the Russian modernist author Mikhail Kuzmin’s long poem “The Trout Breaks the Ice”. The levels are: (1) the grammatical tenses vs. the astronomical time (non-finite verb forms (imperative) are also assumed to indicate time); (2) the meters of this polymetric poem; (3) realistic vs. symbolic and (4) static vs. dynamic narrative modes. The analysis is done by the chapter, and the data are summarized in five tables. It turned out that certain features regularly co-occur, thus supporting the complex composition of the poem. In particular, the present tense and time regularly mark the realistic and static chapters written in various meters, whereas the past tense and time are specific to the realistic and dynamic chapters written in iambic pentameter. The article sheds new light on the compositional structure of Kuzmin’s poem and the general principles of poetic composition.
Best Practices for Information Architecture, Organization, and Retrieval in Digital Language Archives within University Institutional Repositories
Authors: Vann Robert
Published: October 2021

This report presents a case study about building a working digital language archive in a hosted university institutional repository. Best practices in language documentation regarding information architecture, organization, and retrieval are considered in relation to university library commitments to resource acquisition/preservation and online cataloging/delivery systems. Despite challenges, findings suggest that constructing digital language archives in university institutional repositories may offer viable collaborative solutions for researchers unable to find suitable, pre-existing archives in which to deposit their language documentary materials. The report concludes that, in such situations, the ability to satisfy best practices may respond to the strengths/weaknesses of particular software implementations as much as it reflects the design team’s vision, as theory and method in language documentation increasingly become matters of library and information science.
Implicaciones de la metropolización en el eje Cota-Chía-Cajicá. Desafíos de cara a la conformación de la Región Metropolitana Bogotá-Cundinamarca
Authors: Osorio Ardila Giselle Andrea , Rincón Moreno Luz Marina , Muñoz Reyes Javier
Published: October 2021

A partir del caso de tres municipios colindantes con Bogotá, se analizan las particularidades e implicaciones diferenciadas del proceso de metropolización. Se argumenta que las actuales transformaciones no solo obedecen a las dinámicas propias de la urbanización, sino que los pro­cesos históricos y actuales también han tenido origen tanto en decisiones específicas de grupos sociales determinados, como en la falta de decisiones y en la ausencia de coordinación entre entidades territoriales. En ese sentido, la recién conformada Región Metropolitana Bogotá- Cundinamarca puede ser la oportunidad para atender las problemáticas resultantes del proceso de metropolización y solventar algunas de sus falencias. Además, su potencialidad radica en la posibilidad de generar una visión de futuro unificada y la coordinación efectiva entre los instrumentos de planeación, gestión, seguimiento y control del ordenamiento territorial. Para terminar, con base en el análisis de este artículo y como aporte a las discusiones de constitución de la Región Metropolitana, proponemos un cinturón verde entre Bogotá, Cota y Chía, para disminuir la tendencia a la conurbación y a la expansión ininterrumpida de la mancha urbana de Bogotá sobre la Sabana Centro.
Grupo de estudo: um relato de experiência sobre a mediação virtual durante a pandemia do Covid-19
Authors: Maciel Geovânia de Souza Andrade , Oliveira Alyne Pereira de
Published: October 2021

O presente artigo refere-se a um relato de experiência acerca de uma das atividades realizadas por meio do Projeto de Mediação Virtual. Trata-se de um grupo de estudo virtual realizado com alunos dos segundos anos de uma instituição de ensino de Ji-Paraná e de outra instituição pública de ensino situada na cidade vizinha, Ouro Preto do Oeste. O projeto teve como objetivo promover o aprofundamento do processo de aprendizagem por intermédio do ensino remoto, em decorrência da Pandemia de COVID-19. Como aporte teórico a criação do grupo pauta-se nos estudos de Freire (1996), Dayrell (2007) e em especial, na abordagem dos pesquisadores Murphy e Lick (2005). Isto posto, a atividade em pauta realizou-se por meio de um grupo no WhatsApp, onde os 57 participantes formaram uma comunidade com ênfase na troca de conhecimentos. Os resultados do grupo de estudo  mostraram que a dinamização do ensino é fundamental para motivar o processo educacional e promover uma aprendizagem colaborativa.
MEMÓRIA E HISTÓRIA: A CONSTRUÇÃO DO FEMININO EM O ALEGRE CANTO DA PERDIZ, DE PAULINA CHIZIANE
Authors: Silva Luciana Morais da
Published: October 2021

O propósito da presente reflexão é identificar em O alegre canto da perdiz, da escritora Paulina Chiziane, os processos de construção das personagens. O percurso narrativo envereda por traumas e dores pertencentes aos conflitos coloniais e também pelo sofrimento recorrente imputado ao feminino. A proposta foi identificar as gerações de mulheres retratadas na obra e analisar os diversos sentidos existentes em suas vidas. Pretende-se perceber como os traumas coloniais asseveram a condição subserviente da mulher. Sob o olhar de Chiziane, o Moçambique colonial é observado como uma nação a ser explorada e, por isso, o feminino é jogado na obscuridade. A autora celebra a força da mulher, capaz de subverter as mais diversas dores e, por fim, fazer nascer a esperança, principalmente ao se resguardar no sagrado da memória e no combate contras as mazelas que invadiram sua terra.