Application of sequence semantic and integrated cellular geography approach to study alternative biogenesis of exonic circular RNA.

BACKGROUND: Concurrent existence of lncRNA and circular RNA at both nucleus and cytosol within a cell at different proportions is well reported. Previous studies showed that circular RNAs are synthesized in nucleus followed by transportation across the nuclear membrane and the export is primarily defined by their length. lncRNAs primarily originated through inefficient splicing and seem to use NXF1 for cytoplasm export. However, it is not clear whether circularization of lncRNA happens only in nucleus or it also occurs in cytoplasm. Studies indicate that circular RNAs arise when the splicing apparatus undergoes a phenomenon of back splicing. Minor spliceosome (U12 type) mediated splicing occurs in cytoplasm and is responsible for the splicing of 0.5% of introns of human cells. Therefore, possibility of cRNA biogenesis mediated by minor spliceosome at cytoplasm cannot be ruled out. Secondly, information on genes transcribing both circular and lncRNAs along with total number of RBP binding sites for both of these RNA types is extractable from databases. This study showed how these apparently unconnected pieces of reports could be put together to build a model for exploring biogenesis of circular RNA. RESULTS: As a result of this study, a model was built under the premises that, sequences with special semantics were molecular precursors in biogenesis of circular RNA which occurred through catalytic role of some specific RBPs. The model outcome was further strengthened by fulfillment of three logical lemmas which were extracted and assimilated in this work using a novel data analytic approach, Integrated Cellular Geography. Result of the study was found to be in well agreement with proposed model. Furthermore this study also indicated that biogenesis of circular RNA was a post-transcriptional event. CONCLUSIONS: Overall, this study provides a novel systems biology based model under the paradigm of Integrated Cellular Geography which can assimilate independently performed experimental results and data published by global researchers on RNA biology to provide important information on biogenesis of circular RNAs considering lncRNAs as precursor molecule. This study also suggests the possible RBP-mediated circularization of RNA in the cytoplasm through back-splicing using minor spliceosome.

An improved protein structure evaluation using a semi-empirically derived structure property.

BACKGROUND: In the backdrop of challenge to obtain a protein structure under the known limitations of both experimental and theoretical techniques, the need of a fast as well as accurate protein structure evaluation method still exists to substantially reduce a huge gap between number of known sequences and structures. Among currently practiced theoretical techniques, homology modelling backed by molecular dynamics based optimization appears to be the most popular one. However it suffers from contradictory indications of different validation parameters generated from a set of protein models which are predicted against a particular target protein. For example, in one model Ramachandran Score may be quite high making it acceptable, whereas, its potential energy may not be very low making it unacceptable and vice versa. Towards resolving this problem, the main objective of this study was fixed as to utilize a simple experimentally derived output, Surface Roughness Index of concerned protein of unknown structure as an intervening agent that could be obtained using ordinary microscopic images of heat denatured aggregates of the same protein. RESULT: It was intriguing to observe that direct experimental knowledge of the concerned protein, however simple it may be, might give insight on acceptability of its particular structural model out of a confusion set of models generated from database driven comparative technique for structure prediction. The result obtained from a widely varying structural class of proteins indicated that speed of protein structure evaluation can be further enhanced without compromising with accuracy by recruiting simple experimental output. CONCLUSION: In this work, a semi-empirical methodological approach was provided for improving protein structure evaluation. It showed that, once structure models of a protein were obtained through homology technique, the problem of selection of a best model out of a confusion set of Pareto-optimal structures could be resolved by employing a structure agent directly obtainable through experiment with the same protein as experimental ingredient. Overall, in the backdrop of getting a reasonably accurate protein structure of pathogens causing epidemics or biological warfare, such approach could be of use as a plausible solution for fast drug design.

Dosimetric influence of filtered and flattening filter free photon beam on rapid arc (RA) radiotherapy planning in case of cervix carcinoma.

AIM: To investigate the dosimetric influence of filtered and flattening filter free (FFF) photon beam of 6 and 10 MV energies on cervix RA radiotherapy planning and to find possibilities to develop the clinically acceptable RA plans with FFFB photon beam and explore their potential benefits to cervix cancer patients. BACKGROUND: FFF photon beams enhances the treatment delivery by increased dose rate which results in shorter treatment time, this shorter treatment time reduces intrafraction motion and enhance comfort to the patients. MATERIALS AND METHODS: RA plans were generated for filtered and flattening filter free photon beams of 6 and 10 MV energies using same dose-volumes constraints. RA plans were generated to deliver a dose of 50.4 Gy in 28 fractions, for a cohort of eleven patients reported with cervix carcinoma. RA plans were evaluated in terms of PTV coverage, dose to OAR's, CI, HI, total no. of monitor units (MUs) and NTID and low dose volume of normal tissues. RESULTS: Clinically acceptable and similar plans were generated for filtered and flattening filter free photon beams. FFFB delivered slightly higher mean target dose (52.28 Gy vs. 52.0 Gy, p = 0.000 for 6 MV and 52.42 Gy vs. 52.0 Gy, p = 0.000 for 10 MV) less homogeneous (1.062 vs. 1.052, p = 0.000 for 6 MV and 1.066 vs. 1.051, p = 0.000 for 10 MV) and less conformal (1.007 vs. 1.004, p = 0.104 for 6 MV and 1.012 vs. 1.003, p = 0.010 for 10 MV) RA plans compared to FB. FFFB delivered more doses to the bladder and rectum, also required more numbers of MUs in comparison to FB. CONCLUSIONS: This study concludes that FB is more beneficial for cervix RA planning in comparison to FFFB, as FB generates more conformal and homogenous rapid arc plans and offers better OAR's sparing.

Tumour volumes: Predictors of early treatment response in locally advanced head and neck cancers treated with definitive chemoradiation.

AIM: To analyse and predict early response 3 months post definitive chemoradiation (CCRT) utilising tumour volume (TV) measurement in locally advanced head and neck cancers (LAHNC). BACKGROUND: LAHNC are 3-dimentional lesions. The largest diameter of these tumours measured for T-classification may not necessarily reflect the true tumour dimensions. TV accurately reflects the tumour burden because it is a measurement of tumour burden in all three dimensions. MATERIALS AND METHODS: It is a single institutional prospective study including 101 patients with LAHNC treated with definitive CCRT. TV data noted were primary tumour volume (PTV), total nodal volume (TNV) and total tumour volume (TTV). Response evaluation was done at 3 months after the completion of definitive CCRT and patients were categorised either having achieved complete response (CR) or residual disease. RESULTS: Patients who had not achieved CR were found to have larger TV compared with those who had achieved CR. There were significant inverse correlations between PTV and response (median 16.37 cm(3) vs. 45.2 cm(3); p = 0.001), and between TTV and response (median 36.14 cm(3) vs. 66.06 cm(3); p < 0.001). Receiver operating characteristic (ROC) analysis identified an "optimal cut-off" value of 41 cm(3) for PTV and 42 cm(3) for TTV above and below which the magnitude of difference in response was the greatest. CONCLUSIONS: If response evaluation 3 months post CCRT is to be predicted it is simply not enough to measure the largest single dimension of the tumour. TV seems to be a better and more accurate reflection of the true total tumour burden or extent of the disease.

Preclinical Characterization of ARX517, a Site-specific Stable PSMA-Targeted Antibody Drug Conjugate for Treatment of Metastatic Castration-Resistant Prostate Cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is an advanced disease in which patients ultimately fail standard of care androgen-deprivation therapies and exhibit poor survival rates. The prostate-specific membrane antigen (PSMA) has been validated as a mCRPC tumor antigen with over-expression in tumors and low expression in healthy tissues. Using our proprietary technology for incorporating synthetic amino acids (SAAs) into proteins at selected sites, we have developed ARX517, an antibody drug conjugate (ADC) which is composed of a humanized anti-PSMA antibody site-specifically conjugated to a tubulin inhibitor at a drug-to-antibody ratio of 2. After binding PSMA, ARX517 is internalized and catabolized, leading to cytotoxic payload delivery and apoptosis. To minimize premature payload release and maximize delivery to tumor cells, ARX517 employs a non-cleavable PEG linker and stable oxime conjugation enabled via SAA protein incorporation to ensure its overall stability. In vitro studies demonstrate that ARX517 selectively induces cytotoxicity of PSMA-expressing tumor cell lines. ARX517 exhibited a long terminal half-life and high serum exposure in mice, and dose-dependent anti-tumor activity in both enzalutamide-sensitive and -resistant CDX and PDX prostate cancer models. Repeat dose toxicokinetic studies in non-human primates demonstrated ARX517 was tolerated at exposures well above therapeutic exposures in mouse pharmacology studies, indicating a wide therapeutic index. In summary, ARX517 inhibited tumor growth in diverse mCRPC models, demonstrated a tolerable safety profile in monkeys, and had a wide therapeutic index based on preclinical exposure data. Based on the encouraging preclinical data, ARX517 is currently being evaluated in a Phase 1 clinical trial ([NCT04662580]).

TemPred: A Novel Protein Template Search Engine to Improve Protein Structure Prediction.

Among new protein structure predictors, the recently developed AlphaFold predictor relies on contact map in line with contact map potential based threading model that basically relies on fold recognition. In parallel, sequence similarity based homology model relies on homologue recognition. Both of these methods rely on sequence-structure or sequence-sequence similarity with protein with known structure in absence of which, as argued in the development of AlphaFold, the structure prediction becomes quite challenging. However, the term, "known structure" depends on the similarity method adopted to identify it, for example, through sequence match yielding homologue or sequence-structure match yielding a fold. Also, quite often, AlphaFold structures are found to be not acceptable by the structure evaluating gold standard parameters. In this context, this work utilized the concept of ordered local physicochemical property, ProtPCV by Pal et al (2020) providing a new similarity criteria to identify the template protein with known structure. Finally a template search engine, TemPred was developed using the ProtPCV similarity criteria. It was intriguing to find that quite often templates generated by TemPred were better than that produced by the conventional search engines. It pointed out the need of combined approach to get better structural model for a protein.

Analytical comparability to evaluate impact of manufacturing changes of ARX788, an Anti-HER2 ADC in late-stage clinical development.

ARX788 is an anti-HER2 antibody drug conjugate (ADC) developed using Ambrx proprietary Engineered Precision Biologics technology. The manufacturing process of ARX788 has been optimized during the course of early to late-phase clinical development. A comprehensive evaluation of side-by-side comparability between pre- and post-change process for ARX788 drug substance and drug product from a quality perspective was conducted based on ICH Q5E guidelines consisting of batch release assays, physicochemical and biophysical characterization, biological characterization, and forced degradation studies. All results have substantiated a high degree of similarity between the pre- and post-change ARX788 drug substance batches and drug product lots, demonstrating that the process manufacturing changes did not impact product quality.

Rhizobacterial mediated interactions in Curcuma longa for plant growth and enhanced crop productivity: a systematic review.

Turmeric (Curcuma longa L.), a significant commercial crop of the Indian subcontinent is widely used as a condiment, natural dye, and as a cure for different ailments. Various bioactive compounds such as turmerones and curcuminoids have been isolated from C. longa that have shown remarkable medicinal activity against various ailments. However, reduced soil fertility, climatic variations, rapid urbanization, and enhanced food demand, pose a multifaceted challenge to the current agricultural practices of C. longa. Plant growth-promoting microbes play a vital role in plant growth and development by regulating primary and secondary metabolite production. Rhizospheric associations are complex species-specific interconnections of different microbiota with a plant that sustain soil health and promote plant growth through nutrient acquisition, nitrogen fixation, phosphate availability, phytohormone production, and antimicrobial activities. An elaborative study of microbiota associated with the roots of C. longa is essential for rhizospheric engineering as there is a huge potential to develop novel products based on microbial consortium formulations and elicitors to improve plant health, stress tolerance, and the production of secondary metabolites such as curcumin. Primarily, the purpose of this review is to implicate the rhizospheric microbial flora as probiotics influencing overall C. longa health, development, and survival for an increase in biomass, enhanced yield of secondary metabolites, and sustainable crop production.

Down But Not Out: Vasectomy Is Faring Poorly Almost Everywhere-We Can Do Better To Make It A True Method Option.

INTRODUCTION: Demand for vasectomy-1 of 2 contraceptive methods for men-has been low, with deep-seated myths, misconceptions, and provider bias against it widespread. Programmatic attention and donor funding have been limited and sporadic. METHODS: We analyzed vasectomy use in 84 low- and middle-income countries (LMICs) plus the 11 high-income countries with vasectomy prevalence above 1%. These 95 countries comprise 90% of the world's population. Data come from United Nations survey compilations, population estimates, and gender inequality rankings. We also reviewed recent articles on vasectomy and analyses of chronic challenges to vasectomy service provision. RESULTS: Vasectomy use is 61% lower now than 2 decades ago. Of 922 million women using contraception worldwide, 17 million rely on vasectomy-27 million fewer than in 2001. In contrast, 219 million women use tubectomy-8 million more than in 2001. Of 84 LMICs, 7 report vasectomy prevalence above 2%. In 56 LMICs, no more than 1 in 1,000 women relies on vasectomy. Female-to-male disparities in permanent method use widened globally, from 5:1 to 13:1, and are much higher in some regions and countries (e.g., 76:1 in India). Countries with the highest vasectomy prevalence are among those with the highest gender equality and vice versa. CONCLUSION: Vasectomy use is surprisingly low globally and declining. Use remains negligible in almost all LMICs, reflecting low demand and program priority. For vasectomy to become an accessible, rights-based option, program efforts need to be holistic, ensuring an enabling environment while coordinating demand- and service-focused efforts. Vasectomy champions at all levels should be supported on a sustained basis. On the demand side, harnessing mass and social media to increase accurate knowledge and normalize vasectomy as a method and service will be particularly valuable. Evidence from Bolivia suggests relatively few trained providers and procedures could result in a country's attaining 1% vasectomy prevalence.

APT: An Automated Probe Tracker From Gene Expression Data.

Out of currently available semi-automatic tools for detecting diagnostic probes relevant to a pathophysiological condition, ArrayMining and GEO2R of NCBI are most popular. The shortcomings of ArrayMining and GEO2R are that both tools list the probes ordering them on the basis of their individual statistical level of significances with only difference of statistical methods used by them. While the latest tool GEO2R outputs either top 250 or all genes following its own ranking mechanism, ArrayMining requires number of probes to be inputted by the user. This study provided a way for automatic selection of probe-set that can be obtained from the voting of outputs resulted from statistical methods, t-Test, Mann-Whitney Test and Empirical Bayes Moderated t-test. It was also intriguing to find that the parameters of these statistical methods can be represented as a mathematical function of group fisher's discriminant ratio of a disease-control expression data-pair. Result of this fully automatic method, APT shows 88.97 percent success in comparison to 80.40 and 87.60 percent successes of ArrayMining and GEO2R respectively to include reported probes. Furthermore, out of 10 fold cross validation and 5 new test cases, APT shows a better performance than both ArrayMining and GEO2R in regards to sensitivity and specificity.

Understanding factors associated with continuation of intrauterine device use in Gujarat and Rajasthan, India: a cross-sectional household study.

The Government of India has promoted the expansion of access to and uptake of intrauterine devices (IUDs), during both the interval (IIUD) and postpartum (PPIUD) periods, as part of its Family Planning 2020 initiative. This study, conducted by EngenderHealth as part of the Expanding Access to IUD Services in India project, examines IIUD and PPIUD continuation rates over time and investigates factors associated with IUD continuation. We recruited respondents (N = 5024) through a repeated cross-sectional household study between February and December 2019. We identified respondents using IUD client data from public health facility registers in 20 districts of Gujarat and Rajasthan. We compared continuation rates for IIUD and PPIUD adopters and used regression analyses to measure the association between continuation and demographic, quality of care, and counselling variables. IIUD continuation rates decreased from 85.6% to 78.3% and PPIUD rates decreased from 78.5% to 70.7% between month 3 and month 12. Clients experiencing side effects or other problems were 15 times more likely to discontinue IUD use than clients who did not. Clients who received IUD counselling prior to insertion were more likely to continue than those who did not. IUD continuation increased significantly in cases where both partners jointly selected the method compared to situations where women decided alone. Several sociodemographic factors were associated with continuation. Our study demonstrates the value and benefits of programmes offering IUD services emphasising quality counselling and client-centred care to increase access, uptake, and continuation.

Humoral response profiling reveals pathways to prostate cancer progression.

There is considerable evidence for an association between prostate cancer development and inflammation, which results in autoantibody generation against tumor proteins. This immune system-driven amplification of the autoantibody response to intracellular antigens can serve as a sensitive tool to detect low abundance serum proteomic tumor markers for prostate cancer as well as provide insight into biological processes perturbed during cancer development. Here we examine serum humoral responses in a cohort of 34 patients with either benign prostatic hyperplasia or clinically localized prostate cancer (PCa). The experimental strategy couples multidimensional liquid-phase protein fractionation of localized and metastatic prostate cancer tissue lysates to protein microarrays and subsequent mass spectrometry. A supervised learning analysis of the humoral response arrays generated a parsimonious predictor having 78% sensitivity and 75% specificity in distinguishing PCa from benign prostatic hyperplasia in a cohort of American males with elevated prostate-specific antigen. Enrichment analysis of the PCa-specific humoral signature revealed large scale immune reprogramming mediated by STAT transcription factors and the generation of autoantibodies to enzymes involved in nitrogen metabolism. Meta-analysis of independent prostate cancer gene expression data validated the presence of STAT-induced immunomodulation. Concomitant validation of elevated levels of the nitrogen metabolism pathway was obtained by direct measurement of metabolic levels of glutamate and aspartate in prostate cancer tissues. Thus, in addition to functioning as markers in prostate cancer detection, humoral response profiles can serve as powerful tools revealing pathway dysregulation that might otherwise be suppressed by the complexity of the cancer proteome.

ProtPCV: A Fixed Dimensional Numerical Representation of Protein Sequence to Significantly Reduce Sequence Search Time.

Protein sequence is a wealth of experimental information which is yet to be exploited to extract information on protein homologues. Consequently, it is observed from publications that dynamic programming, heuristics and HMM profile-based alignment techniques along with the alignment free techniques do not directly utilize ordered profile of physicochemical properties of a protein to identify its homologue. Also, it is found that these works lack crucial bench-marking or validation in absence of which their incorporation in search engines may appears to be questionable. In this direction this research approach offers fixed dimensional numerical representation of protein sequences extending the concept of periodicity count value of nucleotide types (2017) to accommodate Euclidean distance as direct similarity measure between two proteins. Instead of bench-marking with BLAST and PSI-BLAST only, this new similarity measure was also compared with Needleman-Wunsch and Smith-Waterman. For enhancing the strength of comparison, this work for the first time introduces two novel benchmarking methods based on correlation of "similarity scores" and "proximity of ranked outputs from a standard sequence alignment method" between all possible pairs of search techniques including the new one presented in this paper. It is found that the novel and unique numerical representation of a protein can reduce computational complexity of protein sequence search to the tune of O(log(n)). It may also help implementation of various other similarity-based operation possible, such as clustering, phylogenetic analysis and classification of proteins on the basis of the properties used to build this numerical representation of protein.

The identification of phosphoglycerate kinase-1 and histone H4 autoantibodies in pancreatic cancer patient serum using a natural protein microarray.

Protein microarrays have been used to explore whether a humoral response to pancreatic cancer-specific tumor antigens has utility as a biomarker of pancreatic cancer. To determine if such arrays can be used to identify novel autoantibodies in the sera from pancreatic cancer patients, proteins from a pancreatic adenocarcinoma cell line (MIAPACA) were resolved by 2-D liquid-based separations, and then arrayed on nitrocellulose slides. The slides were probed with serum from a set of patients diagnosed with pancreatic cancer and compared with age- and sex-matched normal subjects. To account for patient-to-patient variability, we used a rank-based non-parametric statistical testing approach in which proteins eliciting significant differences in the humoral response in cancer compared with control samples were identified. The prediction analysis for microarrays classification algorithm was used to explore the classification power of the proteins found to be differentially expressed in cancer and control sera. The generalization error of the classification analysis was estimated using leave-one-out cross-validation. A serum diagnosis of pancreatic cancer in this set was predicted with 86.7% accuracy, with a sensitivity and specificity of 93.3 and 80%, respectively. Candidate autoantibody biomarkers identified using this approach were studied for their classification power by performing a humoral response experiment on recombinant proteins using an independent sample set of 238 serum samples. Phosphoglycerate kinase-1 and histone H4 were noted to elicit a significant differential humoral response in cancer sera compared with age- and sex-matched sera from normal patients and patients with chronic pancreatitis and diabetes. This work demonstrates the use of natural protein arrays to study the humoral response as a means to search for the potential markers of cancer in serum.

Analysis of protein glycosylation and phosphorylation using liquid phase separation, protein microarray technology, and mass spectrometry.

Protein glycosylation and phosphorylation are very common posttranslational modifications. The alteration of these modifications in cancer cells is closely related to the onset and progression of cancer and other disease states. In this protocol, strategies for monitoring the changes in protein glycosylation and phosphorylation in serum or tissue cells on a global scale and specifically characterizing these alterations are included. The technique is based on lectin affinity enrichment for glycoproteins, all liquid-phase two-dimensional fractionation, protein microarray, and mass spectrometry technology. Proteins are separated based on pI in the first dimension using chromatofocusing (CF) or liquid isoelectric focusing (IEF) followed by the second-dimension separation using nonporous silica RP-HPLC. Five lectins with different binding specificities to glycan structures are used for screening glycosylation patterns in human serum through a biotin streptavidin system. Fluorescent phosphodyes and phosphospecific antibodies are employed to detect specific phosphorylated proteins in cell lines or human tissues. The purified proteins of interest are identified by peptide sequencing. Their modifications including glycosylation and phosphorylation could be further characterized by mass-spectrometry-based approaches. These strategies can be used in biological samples for large-scale glycoproteome/phosphoproteome screening as well as for individual protein modification analysis.

Synthesis and structure of [(Ph3P)2Cu(µ-SeCH2Ph)2In(SeCH2Ph)2] as a single-source precursor for the preparation of CuInSe2 nano-materials.

The reaction of freshly prepared Na[In(SeCH2C6H5)4] with the mixture of CuCl and triphenylphosphine in methanol yielded [(PPh3)2CuIn(SeCH2C6H5)4]. The X-ray structure of the complex revealed the monomeric form of [(Ph3P)2Cu(µ-SeCH2Ph)2In(SeCH2Ph)2] consisting of tetrahedral Cu(i) and In(iii) centers, bridged by two benzyl selenolate ligands. The complex on pyrolysis in a furnace or in oleylamine/HDA yielded tetragonal CuInSe2. The morphology and composition of nanostructures were investigated by pXRD, SEM, TEM and EDX analysis. The band gap of the CuInSe2 nanostructures, obtained from pyrolysis in HDA and OA has been deduced from DRS as 1.85 and 1.86 eV, respectively.

Health-related quality of life assessment for head-and-neck cancer patients during and at 3 months after radiotherapy - A prospective, analytical questionnaire-based study.

INTRODUCTION: Health-related quality of life (HRQoL) is a more specific area of QoL that deals with the evaluation and assessment of the impact of the disease and its treatment-related morbidities on a patient's physical, psychological, and social aspects. The aim of the present study was to assess the HRQoL of patients with head-and-neck cancer (HNCs) during and at 3 months after completion of radiotherapy (RT) by intensity-modulated RT. MATERIALS AND METHODS: This study was a prospective, longitudinal, observational, and self-completed questionnaire-based study that included 120 patients with HNC who underwent intensity-modulated RT. The questionnaire had adequate internal consistency. The questionnaires were given to each patient at the beginning of treatment (pretreatment), weekly visits during the course of RT (at the end of 1st, 2nd, 3rd, 4th, 5th, and 6th week), on the day of completion of RT, and then finally at 3 months after completion of RT. Thus, a total of successive nine time points were assessed. RESULTS AND CONCLUSIONS: One hundred and eleven patients completed the questionnaires at all nine time points. HRQoL usually decreases during treatment and then increases to pretreatment levels by 3 months after treatment. The Quality of Life Questionnaire, Core Module and Quality of Life Questionnaire, Head and Neck Module were found to be both valid and reliable. There was a significant QoL reduction for the patients throughout treatment in relation to functions and symptoms in the treatment of HNC. However, all the functions and most of the symptoms returned to baseline at the 3-month follow-up.

Potential for Improving Intrauterine Device (IUD) Service Delivery Quality: Results from a Secondary Data Analysis.

Background: To accelerate progress toward Family Planning 2020 (FP2020) goals, the government of India focused on improving the quality of intrauterine device (IUD) services. EngenderHealth, an international sexual and reproductive health and rights organization, has been supporting the governments of Gujarat and Rajasthan since 2014 through the Expanding Access to IUD Services in India (EAISI) project by building the capacity of service providers, monitoring compliance with standard practices, and strengthening health systems. This study sought to assess whether EAISI-trained providers offer higher quality IUD services than non-EAISI-trained providers, as indicated by a reduction in confirmed IUD complications. Methods: The study team conducted an analytical cross-sectional study of secondary data collected from follow-up registers at 176 intervention facilities (38 in Gujarat and 138 in Rajasthan) during Phase I of the EAISI project. The analysis included follow-up clients who returned to the same facility between April 2018 and March 2019. We performed a multivariate logistic regression to determine factors associated with IUD complications. Results: During the period of assessment, 56,733 clients received IUD insertions, and 10,747 (18.9%) clients returned for follow-up services. Of the returning clients, 49.4% (N=5,305) had received IUDs from EAISI-trained providers, while 50.6% (N=5,442) had received IUDs from non-EAISI-trained providers. A total of 4.0% (N=432) of all returning clients experienced complications (expulsion: 1.3%, missing strings: 1.7%, infection: 1.1%). Clients who received IUDs from non-EAISI-trained providers were 55.5% more likely (95% CI [26.2%, 91.5%], p<0.0005) to have experienced complications than clients who received insertions from EAISI-trained providers. The type of IUD, the timing of the insertion, and the timing of the follow-up visit also affected complication prevalence. Conclusion: Our findings indicate that intensive, practical clinical skills training for IUD insertion can reduce the prevalence of complications.

The use of adaptive intensity-modulated radiotherapy in the treatment of small-cell carcinoma lung refractory to chemotherapy in a patient with preexisting interstitial lung disease.

This is a case report of a 60-year-old diabetic, hypertensive male with a good performance status and a history of bilateral interstitial lung disease with a left upper lobe lung mass diagnosed to be a Stage IIB mixed small-cell/squamous cell carcinoma which was refractory to carboplatin- and etoposide-based chemotherapy. The patient was then taken up for adaptive intensity-modulated radiotherapy with tighter margin under image guidance with a mid-treatment replanning done at 25#. Acute toxicities were assessed weekly and showed no Grade 3 or more reactions. Pulmonary function test showed no detrimental changes during or after radiation. Response assessment at 12 and 20 weeks showed a partial response with decrease in metabolic activity on serial scans.