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In the middle of the 1990s, production of polyester staple fibers amounted to approximately 6 million tons. By the end of 2001, production had grown over 8 million tons, that is 22 percent of all staple fibers produced worldwide. That shift in favor of man-made fibers is also reflected in the Schlafhorst Autocoro spinning plants. In Schlafhorst Autocoro spinning mills in the U.S., polyester has been processed with constant success for almost 20 years. For some years now, the polyester wave has been spilling over across the Pacific into Southeast Asia and China. The pivotal point in the future will be the quality of the polyester fiber. Investigations and tests show that a critical approach beginning from the stage of raw material purchase, by closely examining the chief fiber parameters will set the course for higher productivity and quality in polyester yarn spinning.

We present the preclinical pharmacology of BNT142, a lipid nanoparticle (LNP)-formulated RNA (RNA-LNP) encoding a T cell-engaging bispecific antibody that monovalently binds the T cell marker CD3 and bivalently binds claudin 6 (CLDN6), an oncofetal antigen that is absent from normal adult tissue but expressed on various solid tumors. Upon BNT142 RNA-LNP delivery in cell culture, mice, and cynomolgus monkeys, RNA is translated, followed by self-assembly into and secretion of the functional bispecific antibody RiboMab02.1. In vitro, RiboMab02.1 mediated CLDN6 target cell-specific activation and proliferation of T cells, and potent target cell killing. In mice and cynomolgus monkeys, intravenously administered BNT142 RNA-LNP maintained therapeutic serum concentrations of the encoded antibody. Concentrations of RNA-encoded RiboMab02.1 were maintained longer in circulation in mice than concentrations of directly injected, sequence-identical protein. Weekly injections of mice with BNT142 RNA-LNP in the 0.1- to 1-μg dose range were sufficient to eliminate CLDN6-positive subcutaneous human xenograft tumors and increase survival over controls. Tumor regression was associated with an influx of T cells and depletion of CLDN6-positive cells. BNT142 induced only transient and low cytokine production in CLDN6-positive tumor-bearing mice humanized with peripheral blood mononuclear cells (PBMCs). No signs of adverse effects from BNT142 RNA-LNP administration were observed in mice or cynomolgus monkeys. On the basis of these and other findings, a phase 1/2 first-in-human clinical trial has been initiated to assess the safety and preliminary efficacy of BNT142 RNA-LNP in patients with CLDN6-positive advanced solid tumors (NCT05262530).

Background: Happiness, comfort, and motor function contribute to satisfaction with life for individuals with cerebral palsy (CP). Evidence-based medical care can improve motor function and physical health of youth with CP. Less is known about medical care and its relationship to health-related quality of life (HRQOL) in adolescents and young adults with CP. This study aimed to describe HRQOL among adolescents with CP to examine differences between adolescent (self) and parent (proxy) reports of HRQOL and to explore associations of pain, age, and gross motor function with HRQOL., Methods: This is a retrospective study including adolescents with CP classified as Gross Motor Function Classification System levels I to V, ages 11 to 20 years, reading ≥ a fourth-grade level, and who completed the self-reported Pediatric Outcomes Data Collection Instrument (PODCI). Parents completed the PODCI concurrently or within 12 months and scores were compared. In addition, self-reported scores were compared between age bands, across Gross Motor Function Classification System levels, with typically developing youth (TDY), and between youth with/without pain., Results: PODCI scores from 102 adolescents [59 males; 15.0 (SD: 2.6) years old] were examined. Scores from 50 adolescents and parents were matched. Mean self-reported scores were significantly higher than mean parent-reported scores in 4 domains: upper extremity and physical function ( P =0.018), sports and physical function ( P =0.005), happiness ( P =0.023), and global functioning ( P =0.018). All domains, except Happiness, were significantly < TDY ( P <0.01). The presence of pain was associated with lower scores in all domains ( P <0.05)., Conclusion: Examining HRQOL with the PODCI revealed significant limitations in physical function and higher pain in adolescents with CP compared with TDY. Self- and parent-reported PODCI results should be considered separately. Adolescents report higher HRQOL compared with parent proxy. Recognizing and validating the perspectives of youth and their parents presents an opportunity for providers to discuss different points of view with families. Such engagement can help promote self-efficacy in youth with CP as they transition to the responsibility of guiding their own care in adulthood., Level of Evidence: III, Retrospective comparative study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

IMAB362/Zolbetuximab, a first-in-class IgG1 antibody directed against the cancer-associated gastric-lineage marker CLDN18.2, has recently been reported to have met its primary endpoint in two phase 3 trials as a first-line treatment in combination with standard of care chemotherapy in CLDN18.2-positive Her2 negative advanced gastric cancer. Here we characterize the preclinical pharmacology of BNT141, a nucleoside-modified RNA therapeutic encoding the sequence of IMAB362/Zolbetuximab, formulated in lipid nanoparticles (LNP) for liver uptake. We show that the mRNA-encoded antibody displays a stable pharmacokinetic profile in preclinical animal models, mediates CLDN18.2-restricted cytotoxicity comparable to IMAB362 recombinant protein and inhibits human tumor xenograft growth in immunocompromised mice. BNT141 administration did not perpetrate mortality, clinical signs of toxicity, or gastric pathology in animal studies. A phase 1/2 clinical trial with BNT141 mRNA-LNP has been initiated in advanced CLDN18.2-expressing solid cancers (NCT04683939)., Competing Interests: All authors are current or former employees of, and own stock and/or stock options in, BioNTech SE. Ö.T. is the Chief Medical Officer of BioNTech SE and is named as an inventor on patents related to IMAB362/Zolbetuximab. U.Ş. is the Chief Executive Officer of BioNTech SE. A patent application has been submitted by BioNTech SE for BNT141. H.B-M., U.E., C.R.S., L.F., C.L., J.D., K.B., U.Ş., and Ö.T. are named as inventors on issued or pending patents related to BNT141. U.Ş. and Ö.T. have received royalties and consultancy fees from Astellas Pharma., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Purpose: To examine the role of multiple factors, including therapy dose, on recovery of mobility function during post-single-event multilevel surgery (SEMLS) rehabilitation in youth with cerebral palsy., Methods: Several factors expected to influence postoperative change in Gross Motor Function Measure (GMFM) were examined: age, Gross Motor Function Classification System (GMFCS) level, cognition, number of osteotomies, surgical complications, medical comorbidities, number of therapy sessions, and preoperative measures of gait, balance, and gross motor function., Results: Sixty-nine youth with cerebral palsy, GMFSC levels I-IV, who had undergone SEMLS and rehabilitation had on average 2.6 osteotomies and 89 postoperative therapy sessions. Fewer osteotomies, higher therapy dose, higher preoperative GMFM, and lower GMFM at postoperative admission were significant in determining GMFM change., Conclusions: The most relevant factors on post-SEMLS recovery were therapy dose, surgical burden, and level of gross motor function immediately before and after surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Academy of Pediatric Physical Therapy of the American Physical Therapy Association.)

Aim: To determine how surgical burden and preoperative factors affect the recovery of walking activity after multilevel orthopedic surgery (MLS)., Method: In this retrospective study, inclusion criteria were a diagnosis of cerebral palsy, MLS, and walking activity monitoring using a StepWatch device within 12 months pre-MLS and 24 months post-MLS. The outcome measure was total mean strides per day normalized to age and Gross Motor Function Classification System level. Pre- and postoperative walking activity were compared using unpaired t-tests; the effects of preoperative predictors and surgical burden on the recovery of walking activity were evaluated using regression analysis., Results: Participants included 178 children (mean age 12 years 10 months [SD 8 years 7 months; range 4-20 years]; 91 males, 87 females). On average, children returned to baseline walking activity 3 months after low-burden surgery and 1 year 2 months after high-burden surgery. Postoperative walking activity was higher for children who had surgery at a younger age and those with a higher preoperative mobility function., Interpretation: The burden of MLS was found to be inversely related to the time to recovery of postoperative walking activity. These findings provide evidence to help clinicians set expectations for return to function post-MLS. Further study is necessary to investigate the impact of postoperative factors on walking activity recovery., What This Paper Adds: High-burden surgeries lead to longer recovery than low-burden surgeries. Younger children recover walking activity faster after multilevel orthopedic surgery. Children with high preoperative mobility function recover walking activity faster after surgery., (© 2022 Mac Keith Press.)

Custom made tricalcium phosphate/calcium pyrophosphate bone substitutes with a well-defined architecture were fabricated in this study using 3D powder printing with tricalcium phosphate (TCP) powder and a liquid phase of phosphoric acid. The primary formed matrix of dicalcium phosphate dihydrate (DCPD, brushite) was converted in a second step to calcium pyrophosphate (CPP) by heat treatment in the temperature range 1,100-1,300 degrees C. The structures exhibited compressive strengths between 0.8 MPa and 4 MPa after sintering at 1,100-1,250 degrees C, higher strengths were obtained by increasing the amount of pyrophosphate formed in the matrix due to a post-hardening regime prior sintering as well as by the formation of a glass phase from TCP and calcium pyrophosphate above 1,280 degrees C, which resulted in a strong densification of the samples and compressive strength of >40 MPa.