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The Response Evaluation in Solid Tumors (RECIST) 1.1 provides key guidance for performing imaging response assessment and defines image-based outcome metrics in oncology clinical trials, including progression free survival. In this framework, tumors identified on imaging are designated as either target lesions, non-target disease or new lesions and a structured categorical response is assigned at each imaging time point. While RECIST provides definitions for these categories, it specifically and objectively defines only the target disease. Predefined thresholds of size change provide unbiased metrics for determining objective response and disease progression of the target lesions. However, worsening of non-target disease or emergence of new lesions is given the same importance in determining disease progression despite these being qualitatively assessed and less rigorously defined. The subjective assessment of non-target and new disease contributes to reader variability, which can impact the quality of image interpretation and even the determination of progression free survival. The RECIST Working Group has made significant efforts in developing RECIST 1.1 beyond its initial publication, particularly in its application to targeted agents and immunotherapy. A review of the literature highlights that the Working Group has occasionally employed or adopted objective measures for assessing non-target and new lesions in their evaluation of RECIST-based outcome measures. Perhaps a prospective evaluation of these more objective definitions for non-target and new lesions within the framework of RECIST 1.1 might improve reader interpretation. Ideally, these changes could also better align with clinically meaningful outcome measures of patient survival or quality of life., Competing Interests: Declarations Ethics approval Not applicable. Consent for publication We consent to publish. Competing interests Jonathan Goldin: Founder of MedQIA LLC., (© 2024. The Author(s).)

Repeat expansions in the C9orf72 gene are the most common genetic cause of (ALS) and frontotemporal dementia (FTD). Like other genetic forms of neurodegeneration, pinpointing the precise mechanism(s) by which this mutation leads to neuronal death remains elusive, and this lack of knowledge hampers the development of therapy for C9orf72-related disease. We used an agnostic approach based on genomic data (n = 41,273 ALS and healthy samples, and n = 1,516 C9orf72 carriers) to overcome these bottlenecks. Our drug-repurposing screen, based on gene- and expression-pattern matching and information about the genetic variants influencing onset age among C9orf72 carriers, identified acamprosate, a γ-aminobutyric acid analog, as a potentially repurposable treatment for patients carrying C9orf72 repeat expansions. We validated its neuroprotective effect in cell models and showed comparable efficacy to riluzole, the current standard of care. Our work highlights the potential value of genomics in repurposing drugs in situations where the underlying pathomechanisms are inherently complex. VIDEO ABSTRACT., Competing Interests: Declaration of interests B.J.T. holds patents on clinical testing and therapeutic intervention for the hexanucleotide repeat expansion of C9orf72., (Published by Elsevier Inc.)

Bifunctional electrocatalysts, capable of efficiently driving both the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER), are crucial for advancing electrochemical processes. While noble-metal-based catalysts are widely recognized for their role in oxygen processes, current state-of-the-art designs are limited to either ORR or OER activity, presenting a notable research gap. In addressing this challenge, we have developed a novel Ni/NiO-C nanocomposite catalyst derived from a nickel-based metal-organic framework ( Ni-SKU-5 ). For the ORR, the Ni/NiO-C catalyst exhibits an onset potential of 0.95 V vs RHE in a 1.0 M KOH solution, coupled with a Tafel slope of -99 mV dec -1 at 1600 rpm. Moreover, the catalyst displays excellent stability, maintaining a performance of over 90% after 10 h of continuous reaction. Furthermore, the catalyst proves effective in the OER, boasting an overpotential of 370 mV (at 10 mA cm -2 ) and a Tafel slope of 114 mV dec -1 , highlighting its bifunctionality. The bifunctional overpotential of the Ni/NiO-C composite is measured at 820 mV, surpassing that of the 20% Pt/C electrocatalyst (860 mV), highlighting its potential for practical applications. Comparative experiments establish the origin of the robust bifunctional reactivity toward the conformal hybrid structure, porous framework, and the synergistic effect operating among the constituents of the nanocomposite.

Introduction: The prevalence of underweight in women of reproductive age (WRA) in South Asia remains unacceptably high. Underweight women suffer from lowered immunity, infertility, and a risk of developing non-communicable diseases. In pregnancy, undernutrition results in poor neonatal and maternal outcomes. We present the findings and the management strategy of undernutrition in the preconception and pregnancy phase intervention group in the WING study in low- to lower-middle-income neighborhoods of North India., Methods: We analyzed data from the Women and Infants Integrated Interventions for Growth Study (WINGS) intervention group. In this individually randomized factorial design trial, 13,500 women were enrolled from low to middle-income neighborhoods of Delhi: 6,722 women in the preconception group and 2,640 from the pregnancy group. Food supplements in the form of locally prepared snacks were given to provide necessary calories and protein requirements as per the Body mass index (BMI) during the preconception period and each trimester of pregnancy. The snacks (sweet or savory) and milk or egg as a source of high-quality protein were delivered at home, and intakes were observed. Individual tracking and close monthly monitoring were done for compliance, besides screening and treatment of infections., Results: The enrolled women's mean (SD) age was 24.2 (3.1) years. Approximately 35% of women had a height of < 150 cm, and 50% had schooling >12 years. 17% of women in preconception and 14 % in pregnancy intervention groups were Underweight. Approximately two-thirds of underweight women improved 9-12 months after management in the preconception group, and the same proportion improved 4 weeks after management during pregnancy. The proportion of women with inadequate weight gain (IWG) during pregnancy was higher in women who were underweight during preconception., Discussion: A comprehensive approach to managing undernutrition with high-quality energy-dense food supplementation substantially improved weight gain in women during preconception and pregnancy., Clinical Trial Registration: http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339%26EncHid=%26userName=societyforappliedstudies, identifier: Clinical Trial Registry India #CTRI/2017/06/008908., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dhabhai, Chowdhury, Taneja, Shekhar, Kaur, Mittal, Dewan and Bhandari.)

Importance: Multidomain interventions in pregnancy and early childhood have improved child neurodevelopment, but little is known about the effects of additional preconception interventions., Objective: To evaluate the effect of a multifaceted approach including health; nutrition; water, sanitation, and hygiene (WASH); and psychosocial support interventions delivered during the preconception period and/or during pregnancy and early childhood on child neurodevelopment., Design, Setting, and Participants: In this randomized trial involving low- and middle-income neighborhoods in Delhi, India, 13 500 participants were assigned to preconception interventions or routine care for the primary outcome of preterm births and childhood growth. Participants who became pregnant were randomized to pregnancy and early childhood interventions or routine care. Neurodevelopmental assessments, the trial's secondary outcome reported herein, were conducted in a subsample of children at age 24 months, including 509 with preconception, pregnancy, and early childhood interventions; 473 with preconception interventions alone; 380 with pregnancy and early childhood interventions alone; and 350 with routine care. This study was conducted from November 1, 2000, through February 25, 2022., Interventions: Health, nutrition, psychosocial care and support, and WASH interventions delivered during preconception, pregnancy, and early childhood periods., Main Outcomes and Measures: Cognitive, motor, language, and socioemotional performance at age 24 months, assessed using the Bayley Scales of Infant and Toddler Development 3 tool., Results: The mean age of participants at enrollment was 23.8 years (SD, 3.0 years). Compared with the controls at age 24 months, children in the preconception intervention groups had higher cognitive scores (mean difference [MD], 1.16; 98.3% CI, 0.18-2.13) but had similar language, motor, and socioemotional scores as controls. Those receiving pregnancy and early childhood interventions had higher cognitive (MD, 1.48; 98.3% CI, 0.49-2.46), language (MD, 2.29; 98.3% CI, 1.07-3.50), motor (MD, 1.53; 98.3% CI, 0.65-2.42), and socioemotional scores (MD, 4.15; 98.3% CI, 2.18-6.13) than did controls. The pregnancy and early childhood group also had lower incidence rate ratios (RRs) of moderate to severe delay in cognitive (incidence RR, 0.62; 98.3% CI, 0.40-0.96), language (incidence RR, 0.73; 98.3% CI, 0.57-0.93), and socioemotional (incidence RR, 0.49; 98.3% CI, 0.24-0.97) development than did those in the control group. Children in the preconception, pregnancy, and early childhood intervention group had higher cognitive (MD, 2.60; 98.3% CI, 1.08-4.12), language (MD, 3.46; 98.3% CI, 1.65-5.27), motor (MD, 2.31; 98.3% CI, 0.93-3.69), and socioemotional (MD, 5.55; 98.3% CI, 2.66-8.43) scores than did those in the control group., Conclusions and Relevance: Multidomain interventions during preconception, pregnancy and early childhood led to modest improvements in child neurodevelopment at 24 months. Such interventions for enhancing children's development warrant further evaluation., Trial Registration: Clinical Trials Registry-India CTRI/2017/06/008908.

Background: Local humanitarian workers in low and middle-income countries must often contend with potentially morally injurious situations, often with limited resources. This creates barriers to providing sustainable mental health and psychosocial support (MHPSS) to displaced individuals. Clinical supervision is an often neglected part of ensuring high-quality, sustainable care. The Caring for Carers (C4C) project aims to test the effectiveness and acceptability of online group-based supportive supervision on the well-being of MHPSS practitioners, as well as service-user-reported service satisfaction and quality when working with displaced communities in Türkiye, Syria, and Bangladesh. This protocol paper describes the aim, design, and methodology of the C4C project., Method: A quasi-experimental, mixed-method, community-based participatory research study will be conducted to test the effectiveness of online group-based supportive clinical supervision provided to 50 Syrian and 50 Bangladeshi MHPSS practitioners working with Syrian and Rohingya displaced communities. Monthly data will be collected from the practitioners and their beneficiaries during the active control (six months) and supervision period (16 months over two terms). Outcomes are psychological distress (Kessler-6), burnout (the Copenhagen Burnout Inventory), compassion fatigue, compassion satisfaction, and secondary traumatic stress (Professional Quality of Life Scale), perceived injustice, clinical self-efficacy (Counseling Activity Self-Efficacy Scale), service satisfaction, and quality (Client Satisfaction Questionnaire and an 18-item measure developed in this project). A realist evaluation framework will be used to elucidate the contextual factors, mechanisms, and outcomes of the supervision intervention., Discussion: There is a scarcity of evidence on the role of clinical supervision in improving the well-being of MHPSS practitioners and the quality of service they provide to displaced people. By combining qualitative and quantitative data collection, the C4C project will address the long-standing question of the effectiveness and acceptability of clinical supervision in humanitarian settings., (© 2023. The Author(s).)

Long-read sequencing technologies substantially overcome the limitations of short-reads but have not been considered as a feasible replacement for population-scale projects, being a combination of too expensive, not scalable enough or too error-prone. Here we develop an efficient and scalable wet lab and computational protocol, Napu, for Oxford Nanopore Technologies long-read sequencing that seeks to address those limitations. We applied our protocol to cell lines and brain tissue samples as part of a pilot project for the National Institutes of Health Center for Alzheimer's and Related Dementias. Using a single PromethION flow cell, we can detect single nucleotide polymorphisms with F1-score comparable to Illumina short-read sequencing. Small indel calling remains difficult within homopolymers and tandem repeats, but achieves good concordance to Illumina indel calls elsewhere. Further, we can discover structural variants with F1-score on par with state-of-the-art de novo assembly methods. Our protocol phases small and structural variants at megabase scales and produces highly accurate, haplotype-specific methylation calls., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Hypothyroidism is the commonest endocrine disorder of pregnancy, with known adverse feto-maternal outcomes. There is limited data on population-based prevalence, risk factors and outcomes associated with treatment of hypothyroidism in early pregnancy. We conducted analysis on data from an urban and peri-urban low to mid socioeconomic population-based cohort of pregnant women in North Delhi, India to ascertain the burden, risk factors and impact of treatment, on adverse pregnancy outcomes- low birth weight, prematurity, small for gestational age and stillbirth. This is an observational study embedded within the intervention group of the Women and Infants Integrated Interventions for Growth Study, an individually randomized factorial design trial. Thyroid stimulating hormone was tested in 2317 women in early (9-13 weeks) pregnancy, and thyroxin replacement started hypothyroid (TSH ≥2.5mIU/mL). Univariable and multivariable generalized linear model with binomial family and log link were performed to ascertain risk factors associated with hypothyroidism and association between hypothyroidism and adverse pregnancy outcomes. Of 2317 women, 29.2% (95% CI: 27.4 to 31.1) had hypothyroidism and were started on thyroxin replacement with close monitoring. Overweight or obesity was associated with increased risk (adjusted RR 1.29, 95% CI 1.10 to 1.51), while higher hemoglobin concentration was associated with decreased risk (adjusted RR 0.93, 95% CI 0.88 to 0.98 for each g/dL) for hypothyroidism. Hypothyroid women received appropriate treatment with no increase in adverse pregnancy outcomes. Almost a third of women from low to mid socio-economic population had hypothyroidism in early pregnancy, more so if anemic and overweight or obese. With early screening and adequate replacement, adverse pregnancy outcomes may be avoided. These findings highlight the need in early pregnancy for universal TSH screening and adequate treatment of hypothyroidism; as well as for attempts to reduce pre and peri-conception overweight, obesity and anemia. Clinical trial registration: Clinical trial registration of Women and Infants Integrated Interventions for Growth Study Clinical Trial Registry-India, #CTRI/2017/06/008908; Registered on: 23/06/2017, (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies)., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2023 Dhabhai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The toxicity of any drug against normal cells is a health hazard for all humans. At present, health and disease researchers from all over the world are trying to synthesize designer drugs with diminished toxicity and side effects. The purpose of the present study is to enhance the bioavailability and biocompatibility of gemcitabine (GEM) by decreasing its toxicity and reducing deamination during drug delivery by incorporating it inside the hydrophobic cavity of β-cyclodextrin (β-CD) without affecting the drug ability of the parent compound (GEM). The newly synthesized inclusion complex (IC) was characterized by different physical and spectroscopic techniques, thereby confirming the successful incorporation of the GEM molecule into the nanocage of β-CD. The molecular docking study revealed the orientation of the GEM molecule into the β-CD cavity (-5.40 kcal/mol) to be stably posed for ligand binding. Photostability studies confirmed that the inclusion of GEM using β-CD could lead to better stabilization of GEM (≥96%) for further optical and clinical applications. IC (GEM-β-CD) and GEM exhibited effective antibacterial and antiproliferative activities without being metabolized in a dose-dependent manner. The CT-DNA analysis showed sufficiently strong IC (GEM-β-CD) binding ( K a = 8.1575 × 10 10 ), and this interaction suggests that IC (GEM-β-CD) may possibly exert its biological effects by targeting nucleic acids in the host cell. The newly synthesized biologically active IC (GEM-β-CD), a derivative of GEM, has pharmaceutical development potentiality., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objectives: To assess the diagnostic accuracy of Procalcitonin in maternal serum and umbilical cord blood samples to predict Early onset neonatal sepsis (EONS)., Study Design: It was a Prospective analytical cohort study. Pregnant women ≥ 34 weeks gestation in active labour, with risk factors for EONS were included in the study. Maternal blood samples at recruitment and umbilical cord blood samples after delivery were taken for Total leucocyte count (TLC), high sensitivity C-Reactive Protein (hs-CRP) and Procalcitonin. Newborns were classified into non-infected, suspected and proven infection. Sensitivity, specificity and diagnostic accuracy of maternal and cord blood procalcitonin, TLC and hs-CRP were calculated., Results: A total of 200 women were recruited. Maternal procalcitonin had a superior diagnostic accuracy of 99% compared to maternal TLC and maternal hs-CRP. Also, cord blood procalcitonin had a diagnostic accuracy of 95%., Conclusion: Procalcitonin in both maternal as well as cord blood is a promising biomarker to detect EONS with high diagnostic accuracy., Competing Interests: There are no conflicts of interest., (© 2023 The Authors.)

We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases and 4,132 controls. We discovered, replicated, and validated a deletion in TPCN1 as a novel risk locus for LBD and detected the known structural variants at the C9orf72 and MAPT loci as associated with FTD/ALS. We also identified rare pathogenic structural variants in both LBD and FTD/ALS. Finally, we assembled a catalog of structural variants that can be mined for new insights into the pathogenesis of these understudied forms of dementia., Competing Interests: S.W.S. serves on the Scientific Advisory Council of the Lewy Body Dementia Association and the Multiple System Atrophy Coalition. S.W.S. and B.J.T. receive research support from Cerevel Therapeutics. B.J.T. holds patents on the clinical testing and therapeutic implications of the C9orf72 repeat expansion. H.R.M. is employed by the University College London. In the last 12 months, he reports paid consultancy from Roche and Amylyx; lecture fees/honoraria from BMJ, Kyowa Kirin, and Movement Disorders Society; and research grants from Parkinson’s UK, Cure Parkinson’s Trust, PSP Association, Medical Research Council, and the Michael J Fox Foundation. H.R.M. is a co-applicant on a patent application related to C9orf72 “method for diagnosing a neurodegenerative disease” (PCT/GB2012/052140).

Objectives: To evaluate acceptability, safety, and continuation rates of centchroman following abortion., Study Design: Prospective, observational study. Following spontaneous/induced abortion, women were offered centchroman, 30-mg tablet twice weekly for first 3 months, then once weekly with 1 year of follow-up., Results: Of 120 women who opted for centchroman, continuation rate was 91% at 12 months. There was one case of user failure and one method failure and 26% had infrequent cycles., Conclusions: Centchroman is safe, effective, has good acceptance, and continuation rate post abortion with infrequent menstrual cycles as the main limiting factor for its continuation., Implications: Centchroman, available in Government scheme for contraception, has good acceptance and continuation rate post abortion. Its inclusion in contraceptive choices offered for postabortion contraception can go a long way in spacing of pregnancies, decreasing repeated unintended pregnancies, unsafe abortions, maternal morbidity, and mortality., Competing Interests: Conflicts of interest statement The authors have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Neurofibromatosis type 2 (NF2) is an autosomal dominant Mendelian tumor predisposition disorder caused by germline pathogenic variants in the tumor suppressor NF2. Meningiomas are the second most common neoplasm in NF2, often occurring in multiple intracranial and spinal locations within the same patient. In this prospective longitudinal study, we assessed volumes and growth rates of ten spinal and ten cranial benign meningiomas in seven NF2 patients that concluded with surgical resection and performed whole-exome sequencing and copy-number variant (CNV) analysis of the tumors. Our comparison of the volume and the growth rate of NF2-associated spinal and cranial meningiomas point to the differences in timing of tumor initiation and/or to the differences in tumor progression (e.g., non-linear, saltatory growth) at these two anatomical locations. Genomic investigation of these tumors revealed that somatic inactivation of NF2 is the principal and perhaps the only driver of tumor initiation; and that tumor progression likely occurs via accumulation of CNVs, rather than point mutations. Results of this study contribute to a better understanding of NF2-associated meningiomas clinical behavior and their genetic underpinnings.

Objective: To determine the effect of integrated and concurrent delivery of health, nutrition, water, sanitation and hygiene (WaSH), and psychosocial care interventions during the preconception period alone, during pregnancy and early childhood, and throughout preconception, pregnancy, and early childhood on birth outcomes and linear growth at 24 months of age compared with routine care., Design: Individually randomised factorial trial., Setting: Low and middle income neighbourhoods of Delhi, India., Participants: 13 500 women were randomised to receive preconception interventions (n=6722) or routine care (n=6778). 2652 and 2269 pregnant women were randomised again to receive pregnancy and early childhood interventions or routine care. The analysis of birth outcomes included 1290 live births for the preconception, pregnancy, and early childhood interventions (group A), 1276 for the preconception intervention (group B), 1093 for the pregnancy and early childhood interventions (group C), and 1093 for the control (group D). Children aged 24 months by 30 June 2021 were included in the 24 month outcome analysis (453 in group A, 439 in B, 293 in C, and 271 in D)., Interventions: Health, nutrition, psychosocial care and support, and WaSH interventions were delivered during preconception, pregnancy, and early childhood periods., Main Outcome Measures: The primary outcomes were low birth weight, small for gestational age, preterm, and mean birth weight. At 24 months, the outcomes were mean length-for-age z scores and proportion stunted. Three prespecified comparisons were made: preconception intervention groups (A+B) versus no preconception intervention groups (C+D); pregnancy and early childhood intervention groups (A+C) versus routine care during pregnancy and early childhood (B+D) and preconception, pregnancy, and early childhood interventions groups (A) versus control group (D)., Results: The proportion with low birth weight was lower in the preconception intervention groups (506/2235) than in the no preconception intervention groups (502/1889; incidence rate ratio 0.85, 98.3% confidence interval 0.75 to 0.97; absolute risk reduction -3.80%, 98.3% confidence interval -6.99% to -0.60%). The proportion with low birth weight was lower in the pregnancy intervention groups (502/2096) than in the no pregnancy intervention groups (506/2028) but the upper limit of the confidence interval crossed null effect (0.87, 0.76 to 1.01; -1.71%, -4.96% to 1.54%). There was a larger effect on proportion with low birth weight in the group that received interventions in the preconception and pregnancy periods (267/1141) compared with the control group (267/934; 0.76, 0.62 to 0.91; -5.59%, -10.32% to -0.85%). The proportion stunted at 24 months of age was substantially lower in the pregnancy and early childhood intervention groups (79/746) compared with the groups that did not receive these interventions (136/710; 0.51, 0.38 to 0.70; -8.32%, -12.31% to -4.32%), and in the group that received preconception, pregnancy, and early childhood interventions (47/453) compared with the control group (51/271; 0.49, 0.32 to 0.75; -7.98%, -14.24% to -1.71%). No effect on stunting at 24 months was observed in the preconception intervention groups (132/892) compared with the no preconception intervention groups (83/564)., Conclusions: An intervention package delivered during preconception, pregnancy, and early childhood substantially reduced low birth weight and stunting at 24 months. Pregnancy and early childhood interventions alone had lower but important effects on birth outcomes and 24 month outcomes. Preconception interventions alone had an important effect on birth outcomes but not on 24 month outcomes., Trial Registration: Clinical Trial Registry-India CTRI/2017/06/008908., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Biotechnology Industry Research Assistance Council of the Department of Biotechnology, Government of India and Bill and Melinda Gates Foundation, USA for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Intermediate CAG (polyQ) expansions in the gene ataxin-2 (ATXN2) are now recognized as a risk factor for amyotrophic lateral sclerosis. The threshold for increased risk is not yet firmly established, with reports ranging from 27 to 31 repeats. We investigated the presence of ATXN2 polyQ expansions in 9268 DNA samples collected from people with amyotrophic lateral sclerosis, amyotrophic lateral sclerosis with frontotemporal dementia, frontotemporal dementia alone, Lewy body dementia and age matched controls. This analysis confirmed ATXN2 intermediate polyQ expansions of ≥31 as a risk factor for amyotrophic lateral sclerosis with an odds ratio of 6.31. Expansions were an even greater risk for amyotrophic lateral sclerosis with frontotemporal dementia (odds ratio 27.59) and a somewhat lesser risk for frontotemporal dementia alone (odds ratio 3.14). There was no increased risk for Lewy body dementia. In a subset of 1362 patients with amyotrophic lateral sclerosis with complete clinical data, we could not confirm previous reports of earlier onset of amyotrophic lateral sclerosis or shorter survival in 25 patients with expansions. These new data confirm ≥31 polyQ repeats in ATXN2 increase the risk for amyotrophic lateral sclerosis, and also for the first time show an even greater risk for amyotrophic lateral sclerosis with frontotemporal dementia. The lack of a more aggressive phenotype in amyotrophic lateral sclerosis patients with expansions has implications for ongoing gene-silencing trials for amyotrophic lateral sclerosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients with chronic tuberculous empyema and destroyed lung on a prolonged intercostal tube with failed lung expansion considered unsuitable for single-lung ventilation have poor outcomes. The study's objective was to analyze the surgical outcomes and lung expansion factors in these patients following the open window thoracostomy (OWT) procedure., Methods: In a prospective study, patients (males = 63, females = 12) diagnosed with tuberculosis who underwent OWT were analyzed between 2017 and 2018. Factors including age, sex, side, comorbidities, body mass index (BMI), bacteriological culture, and patency of OWT site were evaluated for lung expansion., Results: Mean preoperative weight 40.96 ± 5.70 kg increased significantly postoperatively. Pseudomonas aeruginosa (30.66%) was the most typical organism isolated and smoking (21.3%) was the common risk factor. At 6-month follow-up, complete lung expansion was noted in 60% of patients, while partial and no expansion is seen in 17.3% and 22.3% patients. Similarly 82.4% patients with pre-operative BMI>18.5 kg/m 2 had complete lung expansion, while with BMI < 18.5 kg/m 2 , 41.7% and 45.8% had partial and no-expansion. Complete lung expansion was seen in 97.1%, 18.2%, and 23.1% of patients with obliterated OWT, sputum, and pleural pus positive for acid-fast bacilli (active disease), while in 57.9% of patients with comorbidities, complete lung expansion was absent., Conclusion: The analysis of various factors concludes that lung expansion is not affected by age, sex, side of the disease, and co-morbid conditions; however, extensively diseased lungs with low BMI and positive bacteriological culture, especially P. aeruginosa , active disease, smoking, and patent OWT, interfered with the expansion of the lung.

Treatment response assessment by imaging plays a vital role in evaluating changes in solid tumors during oncology therapeutic clinical trials. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is the reference standard imaging response criteria and provides details regarding image acquisition, image interpretation and categorical response classification. While RECIST 1.1 is applied for the majority of clinical trials in solid tumors, other criteria and modifications have been introduced when RECIST 1.1 outcomes may be incomplete. Available criteria beyond RECIST 1.1 can be explored in an algorithmic fashion dependent on imaging modality, tumor type and method of treatment. Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) is available for use with PET/CT. Modifications to RECIST 1.1 can be tumor specific, including mRECIST for hepatocellular carcinoma and mesothelioma. Choi criteria for gastrointestinal stromal tumors incorporate tumor density with alterations to categorical response thresholds. Prostate Cancer Working Group 3 (PCWG3) imaging criteria combine RECIST 1.1 findings with those of bone scans. In addition, multiple response criteria have been created to address atypical imaging responses in immunotherapy., (© 2022 The Authors. Published by Elsevier Ltd.)

Acquiring an optically transparent feature on the wideband frequency selective surface (FSS), particularly for smart city applications (building window and transportation services) and vehicle windows, is a challenging task. Hence, this study assessed the performance of optically transparent mosaic frequency selective surfaces (MFSS) with a conductive metallic element unit cell that integrated Koch fractal and double hexagonal loop fabricated on a polycarbonate substrate. The opaque and transparent features of the MFSS were studied. While the study on opaque MFSS revealed the advantage of having wideband responses, the study on transparent MFSS was performed to determine the optical transparency application with wideband feature. To comprehend the MFSS design, the evolutionary influence of the unit cell on the performance of MFSS was investigated and discussed thoroughly in this paper. Both the opaque and transparent MFSS yielded wideband bandstop and bandpass responses with low cross-polarisation (-37 dB), whereas the angular stability was limited to only 25°. The transparent MFSS displayed high-level transparency exceeding 70%. Both the simulated and measured performance comparison exhibited good correlation for both opaque and transparent MFSS. The proposed transparent MFSS with wideband frequency response and low cross-polarisation features signified a promising filtering potential in multiple applications.

Background: The burden of gestational diabetes mellitus (GDM) appears to be increasing in India and may be related to the double burden of malnutrition. The population-based incidence and risk factors of GDM, particularly in lower socio-economic populations, are not known. We conducted analyses on data from a population-based cohort of pregnant women in South Delhi, India, to determine the incidence of GDM, its risk factors and association with adverse pregnancy outcomes (stillbirth, preterm birth, large for gestational age babies) and need for caesarean section., Methods: We analyzed data from the intervention group of the Women and Infants Integrated Interventions for Growth Study (WINGS), an individually randomized factorial design trial. An oral glucose tolerance test (OGTT) was performed at the time of confirmation of pregnancy, and for those who had a normal test (≤140 mg), it was repeated at 24-28 and at 34-36 weeks. Logistic regression was performed to ascertain risk factors associated with GDM. Risk ratios (RR) were calculated to find association between GDM and adverse pregnancy outcomes and need for caesarean section., Results: 19.2% (95% CI: 17.6 to 20.9) pregnant women who had at least one OGTT were diagnosed to have GDM. Women who had prediabetes at the time of confirmation of pregnancy had a significantly higher risk of developing GDM (RR 2.08, 95%CI 1.45 to 2.97). Other risk factors independently associated with GDM were woman's age (adjusted OR (AOR) 1.10, 95% CI 1.06 to 1.15) and BMI (AOR 1.04, 95% CI 1.01 to 1.07). Higher maternal height was found to be protective factor for GDM (AOR 0.98, 95% CI 0.96 to 1.00). Women with GDM, received appropriate treatment did not have an increase in adverse outcomes and no increased need for caesarean section CONCLUSIONS: A substantial proportion of pregnant women from a low to mid socio-economic population in Delhi had GDM, with older age, higher BMI and pre-diabetes as important risk factors. These findings highlight the need for interventions for prevention and provision of appropriate management of GDM in antenatal programmes., Clinical Trial Registration: Clinical Trial Registry - India, #CTRI/2017/06/008908 ( http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies )., (© 2022. The Author(s).)

A homozygous AAGGG repeat expansion within the RFC1 gene was recently described as a common cause of CANVAS syndrome. We examined 1069 sporadic ALS patients for the presence of this repeat expansion. We did not discover any carriers of the homozygous AAGGG expansion in our ALS cohort, indicating that this form of RFC1 repeat expansions is not a common cause of sporadic ALS. However, our study did identify a novel repeat conformation and further expanded on the highly polymorphic nature of the RFC1 locus., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Drug discovery and approval in oncology is mediated by the use of imaging to evaluate drug efficacy in clinical trials. Imaging is performed while patients receive therapy to evaluate their response to treatment. Response criteria, specifically Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), are standardized and can be used at different time points to classify response into the categories of complete response, partial response, stable disease, or disease progression. At the trial level, categorical responses for all patients are summated into image-based trial endpoints. These outcome measures, including objective response rate (ORR) and progression-free survival (PFS), are characteristics that can be derived from imaging and can be used as surrogates for overall survival (OS). Similar to OS, ORR and PFS describe the efficacy of a drug. U.S. Food and Drug Administration (FDA) regulatory approval requires therapies to demonstrate direct evidence of clinical benefit, such as improved OS. However, multiple programs have been created to expedite drug approval for life-threatening illnesses, including advanced cancer. ORR and PFS have been accepted by the FDA as adequate predictors of OS on which to base drug approval decisions, thus substantially shortening the time and cost of drug development (1). Use of imaging surrogate markers for drug approval has become increasingly common, accounting for more than 90% of approvals through the Accelerated Approval Program and allowing for use of many therapies which have altered the course of cancer. Keywords: Oncology, Tumor Response  RSNA, 2021.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered., Competing Interests: Declaration of Interests S.P.-B., A.B.S., J.A.H., H.R.M., and B.J.T. hold US, EU, and Canadian patents on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion of C9 or f72. S.W.S. serves on the scientific advisory council of the Lewy Body Dementia Association and is an editorial board member for the Journal of Parkinson’s Disease. B.J.T. is an editorial board member for JAMA Neurology, JNNP, and Neurobiology of Aging. V.S. is on the journal editorial boards of Amyotrophic Lateral Sclerosis, European Neurology, American Journal of Neurodegenerative Diseases, and Frontiers in Neurology. He has also received compensation for consulting services and speaking activities from AveXis, Cytokinetics, Italfarmaco, and Zambon. J.B.R. is an editor for Brain and has received compensation for consulting services from Asceneuron, Biogen, UCB, Astex, and SV Health. J.E.L. is a member of the scientific advisory board for Cerevel Therapeutics and a consultant and provides expert testimony for Perkins Coie., (Published by Elsevier Inc.)