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Cancer is a leading cause of disease burden globally, with more than 19·3 million cases and 10 million deaths recorded in 2020. Research is crucial to understanding the determinants of cancer and the effects of interventions, and to improving outcomes. We aimed to analyse global patterns of public and philanthropic investment in cancer research. In this content analysis, we searched the UberResearch Dimensions database and Cancer Research UK data for human cancer research funding awards from public and philanthropic funders between Jan 1, 2016, and Dec 31, 2020. Included award types were project and programme grants, fellowships, pump priming, and pilot projects. Awards focused on operational delivery of cancer care were excluded. Awards were categorised by cancer type, cross-cutting research theme, and research phase. Funding amount was compared with global burden of specific cancers, measured by disability-adjusted life-years, years lived with disability, and mortality using data from the Global Burden of Disease study. We identified 66 388 awards with total investment of about US$24·5 billion in 2016–20. Investment decreased year-on-year, with the largest drop observed between 2019 and 2020. Pre-clinical research received 73·5% of the funding across the 5 years ($18 billion), phase 1–4 clinical trials received 7·4% ($1·8 billion), public health research received 9·4% ($2·3 billion), and cross-disciplinary research received 5·0% ($1·2 billion). General cancer research received the largest investment ($7·1 billion, 29·2% of the total funding). The most highly funded cancer types were breast cancer ($2·7 billion [11·2%]), haematological cancer ($2·3 billion [9·4%]), and brain cancer ($1·3 billion [5·5%]). Analysis by cross-cutting theme revealed that 41·2% of investment ($9·6 billion) went to cancer biology research, 19·6% ($4·6 billion) to drug treatment research, and 12·1% ($2·8 billion) to immuno-oncology. 1·4% of the total funding ($0·3 billion) was spent on surgery research, 2·8% ($0·7 billion) was spent on radiotherapy research, and 0·5% ($0·1 billion) was spent on global health studies. Cancer research funding must be aligned with the global burden of cancer with more equitable funding for cancer research in low-income and middle-income countries (which account for 80% of cancer burden), both to support research relevant to these settings, and build research capacity within these countries. There is an urgent need to prioritise investment in surgery and radiotherapy research given their primacy in the treatment of many solid tumours. None.

The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However, several reports of non-syndromic/isolated tooth agenesis have also been found in the literature. The characteristic features of hypohidrotic ectodermal dysplasia (HED) comprise of hypodontia/oligodontia, along with hypohidrosis/anhidrosis, and hypotrichosis. Pathogenic variants in EDA, EDAR, EDARADD, and TRAF6, cause the phenotypic expression of HED. Genetic alterations in EDA and WNT10A cause particularly non-syndromic/isolated oligodontia. In the current project, we recruited 57 patients of 17 genetic pedigrees (A-Q) from different geographic regions of the world, including Pakistan, Egypt, Saudi Arabia, and Syria. The molecular investigation of different syndromic and non-syndromic dental conditions, including hypodontia, oligodontia, generalized odontodysplasia, and dental crowding was carried out by using exome and Sanger sequencing. We have identified a novel missense variant (c.311G>A; p.Arg104His) in WNT10A in three oligodontia patients of family A, two novel sequence variants (c.207delinsTT, p.Gly70Trpfs*25 and c.1300T>G; p.Try434Gly) in EDAR in three patients of family B and four patients of family C, respectively. To better understand the structural and functional consequences of missense variants in WNT10A and EDAR on the stability of the proteins, we have performed extensive molecular dynamic (MD) simulations. We have also identified three previously reported pathogenic variants (c.1076T>C; p.Met359Thr), (c.1133C>T; p.Thr378Met) and (c.594_595insC; Gly201Argfs*39) in EDA in family D (four patients), E (two patients) and F (one patient), correspondingly. Presently, our data explain the genetic cause of 18 syndromic and non-syndromic tooth agenesis patients in six autosomal recessive and X-linked pedigrees (A-F), which expand the mutational spectrum of these unique clinical manifestations.

Development of novel materials for organic solar cells is a booming area of current research. Fused-ring electron accepters are the potential agents of revolution in organic photovoltaic devices and revealing high efficiency in organic solar cells. This study highlights the novel quad-rotor-shaped molecules as first example of efficient fused-ring non-fullerene acceptor materials with proficient photovoltaic parameters for their utilization in high-performance organic solar cells. First time, eight quad-rotor-shaped fused-ring electron accepters ( QRFR-1–QRFR-8 ) are developed via modulating end-caps of experimentally synthesized ( BFTT-TN ) molecule ( QRFR ). Optoelectronic properties of proposed molecules are determined using frontier molecular orbitals (FMO), UV–Visible, density of state (DOS), overlap DOS (ODOS), transition density matrix (TDM) heat maps, open circuit voltage (V oc ), binding energies (E b ), reorganization energy of electron (λ e ), hole (λ h ), charge transfer analysis, and compared with reference QRFR . All proposed fused-ring electron accepters disclose less energy gap and λ max in near IR region than QRFR after end-capped engineering. Highest V oc with respect to HOMO PM6 –LUMO acceptor is found 1.66 V in QRFR-6 than QRFR (1.63 V). E b values of QRFR-1 – QRFR-8 are found better and comparable with QRFR . The λ e is found smaller than QRFR in all molecules except QRFR-5 . The proposed quad-rotor-shaped molecules exhibit proficient photovoltaic features and can serve as best candidate for organic solar cells when blended with PM6 film. This study not only enlightens the researchers to use end-capped reforms as effective tactic for designing materials, but also provides novel quad-rotor-shaped materials to experimentalist for synthesis and their usage in future application of organic solar cells. Graphical abstract

The purpose of this study is to identify the Fintech driven operational risk events as no historical data is available. For this, the study reviews the literature to list down possible OR events which may trigger OR in banks, having collaboration with Fintech firms. In second phase, banks' operational risk analysts and managers are asked to give their opinion on the 23 potential OR triggering events in the form of experts' questionnaire. In next phase, after collecting questionnaires back from experts, Lawshe's approach is applied and Content Validity Ratio (CVR) is calculated. As a result, 18 items having CVR greater than cutoff value of 0.42 are retained as valid and contextual in identifying Fintech driven operational risk. The results of study are significantly important for banks adopting Fintech nosiness model led innovative financial products and services to identify new risk and review their existing operational risk management framework, besides giving the regulators an insight into reviewing Regtech processes to inculcate the Fintech driven changes in processes and business models.

Several herbicides, especially paraquat, are persistent organic pollutants which cause damage to humans and animals through reactive oxygen and nitrogen species. Prosopis cineraria (L.) Druce exhibits antioxidant activity and can effectively manage tremors. Therefore, the present research assessed the preventive effect of Prosopis cineraria (L.) Druce ethanolic extract (PCDE) against paraquat-induced toxicity in prepubertal mice. The plant extract was chemically characterized by a high-performance liquid chromatography-diode array detector (HPLC-DAD). The PCDE was orally administered to prepubertal mice for continuous 21 days, 2 h before paraquat exposure (2 mg/kg for consecutive 3 days per week for 3 weeks). The changes in behavior, motor coordination, memory, muscle movement, anxiety, and neurotransmitter levels in the brain were assessed. Histopathology and estimation of oxidative stress parameters in the brain, liver, kidney, and heart tissues were also carried out. HPLC-DAD analysis showed a high amount of quercetin, kaempferol, and ellagic acid derivatives in the plant extract. The PCDE showed improved muscle coordination, muscle movement and memory, and reduced anxiety in prepubertal mice. Moreover, levels of dopamine and noradrenaline were increased in the brain. It successfully ameliorated the oxidative stress in different organs by increasing the level of glutathione and superoxide dismutase and by reducing malondialdehyde. The histopathological assessment showed the plant extract effectively mitigated paraquat-induced pathological lesions in the neurons, neuroglia, hepatocytes, and kidney tissues. It is concluded from the present study that the treatment with PCDE had prevented the paraquat-induced toxicity in the brain, liver, kidney, and heart through the reduction of oxidative stress possibly due to the presence of phenolic compounds and flavonoids.

Several herbicides, especially paraquat, are persistent organic pollutants which cause damage to humans and animals through reactive oxygen and nitrogen species. Prosopis cineraria (L.) Druce exhibits antioxidant activity and can effectively manage tremors. Therefore, the present research assessed the preventive effect of Prosopis cineraria (L.) Druce ethanolic extract (PCDE) against paraquat-induced toxicity in prepubertal mice. The plant extract was chemically characterized by a high-performance liquid chromatography-diode array detector (HPLC-DAD). The PCDE was orally administered to prepubertal mice for continuous 21 days, 2 h before paraquat exposure (2 mg/kg for consecutive 3 days per week for 3 weeks). The changes in behavior, motor coordination, memory, muscle movement, anxiety, and neurotransmitter levels in the brain were assessed. Histopathology and estimation of oxidative stress parameters in the brain, liver, kidney, and heart tissues were also carried out . HPLC-DAD analysis showed a high amount of quercetin, kaempferol, and ellagic acid derivatives in the plant extract. The PCDE showed improved muscle coordination, muscle movement and memory, and reduced anxiety in prepubertal mice. Moreover, levels of dopamine and noradrenaline were increased in the brain. It successfully ameliorated the oxidative stress in different organs by increasing the level of glutathione and superoxide dismutase and by reducing malondialdehyde. The histopathological assessment showed the plant extract effectively mitigated paraquat-induced pathological lesions in the neurons, neuroglia, hepatocytes, and kidney tissues. It is concluded from the present study that the treatment with PCDE had prevented the paraquat-induced toxicity in the brain, liver, kidney, and heart through the reduction of oxidative stress possibly due to the presence of phenolic compounds and flavonoids.

Objectives: To determine patient satisfaction and factors affecting patient satisfaction with laboratory services in Azad Jammu & Kashmir (AJK). Study Design: Cross-sectional study. Place and Duration of Study: Seven District Headquarter Hospitals, DHQ Neelum, DHQ Hattian Bala, DHQ Pallandari, DHQ Bagh, DHQ Kotli, DHQ Bhimber and DHQ Mirpur, Kashmir Pakistan from Dec 2019 to Feb 2020. Methodology: The patients who were referred from the Outdoor Patient Department of the hospital for undergoing investigative tests were included, and patients of age less than 18 and critically ill patients were excluded. Results: The total number of respondents included in the study was 400, with the median score of patient satisfaction with laboratory services being 59 (19), ranging from 32 to 100. Statistically significant disparities in client satisfaction were observed in different DHQ hospitals (p-value=0.01) with Mirpur (63) and Pallandri (40) showing the extreme variation. Residential area, age, and education level were also identified as statistically significant determinants of patient satisfaction (p-value <0.05). Conclusion: patient satisfaction with laboratory services in public hospitals of AJK was very low, and targeted strategies are needed to improve the overall quality of these services.

Interferon with ribavirin is the recommended treatment for chronic hepatitis C with a response rate ranging from 50-80% in different countries. Although sustained response is comparable to clinical cure, but whether interferon therapy slows down the disease process in non-responders and relapsers is not known. To determine the long term outcome of chronic HCV patients who have completed the interferon therapy and compare results between responders, relapsers and non-responders. Retrospective case record analysis of chronic hepatitis C patients who were treated with conventional interferon and ribavirin for 6 months during 1998 to 2002 and their follow up till 2011 were included. Depending upon the response they were divided into three groups i.e. responders, non responders and relapsers. A total of 175 patients were included. There were 126 (72%) males and 49 (28%) females, whose ages ranged from 11 to 70 years (mean 35.8 ± 10.3). After interferon therapy, 109 were sustained responders, 33 were relapsers and 33 non responders. Mean age of the responders (32.4 ± 8.8 years) was significantly less as compared to non responders (40.4 ± 12.0 years) and relapsers (42.4 ±_8.0 years), (p < 0.05). Responders had a much better follow up i.e four years as compared to non responders which was statistically significant (p <0.05). During 10 years follow up, cirrhosis developed in 3 (2.8%) sustained responders, 6 (18.2%) non responders and 8 (24.2%) relapsers. During yearly followup, sustained responders had significantly lower mean ALT and AFP levels as compared to non responders and relapsers (p < 0.05) while non responders and relapsers had lower albumin levels as compared to the responders (p < 0.05). Majority of the sustained responders had disease eradication, but non responders and relapsers should be followed for any evidence of cirrhosis.

Intercanine width, intermolar width and arch length are essential for diagnosis and treatment planning and are closely related factors in orthodontics.The purpose of this study was to determine the correlation between these measurements and how these measurements are related to each other. Dental casts of 100 orthodontic patients (72 females and 28 males) with a mean age of 18.7 years (12-38 years) in the permanent dentition attending the orthodontic department of the University of Lahore, Lahore, Pakistan were randomly selected. The casts were photocopied 1/1 with maximum contrast. Measurements were made on the photocopies of the upper and lower dental casts. Correlation between variables was determined using spearman's rho correlation coefficient. The data showed very high correlation between intercanine width and intermolar width of both upper and lower arches and a weak correlation was observed between upper intercanine width and upper arch length as well as lower arch length. Correlation was significant between upper and lower arch lengths. [PUBLICATION ABSTRACT]