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Vitis vinifera L., commonly known as grape is a major fruit crop in the world. Grapes seem to confer health benefits due to their chemical components, biological and antioxidant activities. The present study is conducted to evaluate the biochemical constituents, antioxidant, and antimicrobial potential of ethanolic grape peduncles (EGP) extract. The result of phytochemical analysis revealed the presence of various phytochemicals such as flavonoid, tannin, carbohydrates, alkaloids, cardiac glycoside, phenol, steroid, terpenoids, quinones and anthraquinones. Furthermore, total phenolic content (TPC) and total flavonoid contents (TFC) were 7.35 ± 0.25 mg GAE/g (Gallic Acid Equivalent per gram) and 29.67 ± 0.13 mg QE/g (Quercetin Equivalent per gram) respectively. DPPH (2, 2-diphenyl-1-picrylhydrazyl) free radical scavenging assay revealed IC 50  = 159.3 μg/mL. The antibacterial and antifungal study disclosed that the extract was highly potent against Salmonella typhi with maximum zone of inhibition of 27.2 ± 1.60 mm and Epidermophyton floccosum with 74 ± 1.81% inhibition. The extract was analyzed for its cytotoxicity and antileishmanial activity and showed no activity against HeLa cell line and promastigotes of Leishmania major. Elements Fe, Mn, Ni, Pb and Cd were determined by atomic absorption spectroscopy and approximately 50 compounds were identified by Gas Chromatography-Mass Spectrometry (GC-MS). Current work suggest that grape peduncles can be a promising source of bioactive medicinal component., (© 2023. The Author(s).)

Objective: We evaluated the epidemiology, manifestations, serology, comorbidities, and survival among patients with systemic sclerosis (SSc) with and without sarcoidosis., Methods: We conducted a retrospective cohort study comparing patients with SSc with and without sarcoidosis. All patients fulfilled the American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for SSc. Sarcoidosis was based on physician diagnosis and/or confirmatory biopsy. The primary outcome was time from diagnosis to all-cause mortality. Survival was evaluated using Kaplan-Meier curves., Results: We included 1977 patients (1971 with SSc, 6 with SSc-sarcoidosis) with a SSc-sarcoidosis prevalence of 0.30%. Sarcoidosis frequently preceded SSc (66.66%). The most frequent sarcoidosis manifestations were pulmonary (66.66%), lymphadenopathy (66.66%), arthritis (50%), cutaneous (33.33%), and hepatic (16.66%). Patients with SSc and SSc-sarcoidosis had female to male sex ratios of 4.5:1 vs 5:1 and median ages of SSc onset of 48.3 vs 43.8 years, respectively. Interstitial lung disease (35% vs 66.66%) and pulmonary hypertension (24.91% vs 50%) tended to occur more frequently whereas abnormal nailfold capillaries (34.7% vs 16.66%) and digital ulcers (33.33% vs 16.66%) tended to occur less frequently among patients with SSc-sarcoidosis, but the differences were not significant. There was an increased frequency of stroke among the patients with SSc-sarcoidosis (relative risk 8.59, 95% CI 1.02-72.00). The median survival times were 23.4 years for SSc-sarcoidosis and 18.6 years for SSc, with no differences in survival curves (log-rank test, P = 0.55)., Conclusion: Sarcoidosis in SSc is rare but appears to occur more frequently than in the general population. It is associated with pulmonary, lymph node, cutaneous, joint, and hepatic involvement. Stroke occurs more frequently in patients with SSc-sarcoidosis but with no differences in survival., (Copyright © 2023 by the Journal of Rheumatology.)

Two novel benzimidazole ligands ( E )-2-((4-(1 H -benzo[ d ]imidazole-2-yl)phenylimino)methyl)-6-bromo-4-chlorophenol (L 1 ) and ( E )-1-((4-(1 H -benzo[ d ]imidazole-2-yl)phenylimino)methyl)naphthalene-2-ol (L 2 ) with their corresponding Cu(ii), Ni(ii), Pd(ii) and Zn(ii) complexes were designed and synthesized. The compounds were characterized by elemental, IR, and NMR ( 1 H & 13 C) spectral analyses. Molecular masses were determined by ESI-mass spectrometry, and the structure of ligand L 1 was confirmed by single crystal X-ray diffraction analysis. Molecular docking was carried out for the theoretical investigation of DNA binding interactions. The results obtained were verified experimentally by UV/Visible absorption spectroscopy in conjunction with DNA thermal denaturation studies. It was observed that ligands (L 1 and L 2 ) and complexes (1-8) were moderate to strong DNA binders, as evident from the binding constants ( K b ). The value was found to be highest for complex 2 (3.27 × 10 5 M -1 ) and lowest for 5 (6.40 × 10 3 M -1 ). A cell line study revealed that breast cancer cells were less viable to the synthesized compounds compared to that of standard drugs, cisplatin and doxorubicin, at the same concentration. The compounds were also screened for in vitro antibacterial activity for which complex 2 showed a promising broad-spectrum effect against all tested strains of bacteria, almost in the proximity of the reference drug kanamycin, while the rest of the compounds displayed activity against selected strains., Competing Interests: Authors have no conflict of interest for this research work., (This journal is © The Royal Society of Chemistry.)

The development of recombinant DNA technology during the past thirty years has enabled scientists to isolate, characterize, and manipulate a myriad of different animal, bacterial, and plant genes. This has, in turn, led to the commercialization of hundreds of useful products that have significantly improved human health and well-being. Commercially, these products have been mostly produced in bacterial, fungal, or animal cells grown in culture. More recently, scientists have begun to develop a wide range of transgenic plants that produce numerous useful compounds. The perceived advantage of producing foreign compounds in plants is that compared to other methods of producing these compounds, plants seemingly provide a much less expensive means of production. A few plant-produced compounds are already commercially available; however, many more are in the production pipeline.

Systemic sclerosis is a systemic autoimmune rheumatic disease characterized by immune abnormalities, leading to vasculopathy and fibrosis. Autoantibody testing has become an increasingly important part of diagnosis and prognostication. Clinicians have been limited to antinuclear antibody (ANA), antitopoisomerase I (also known as anti-Scl-70) antibody, and anticentromere antibody testing. Many clinicians now have improved access to an expanded profile of autoantibody testing. In this narrative review article, we review the epidemiology, clinical associations, and prognostic value of advanced autoantibody testing in people with systemic sclerosis.

Background: Elevated levels of interferons (IFNs) are a characteristic feature of systemic autoimmune rheumatic diseases (SARDs) and may be useful in predicting impending symptomatic progression in anti-nuclear antibody-positive (ANA + ) individuals lacking a SARD diagnosis. Typically, these are measured by their effect on gene expression in the blood, which has limited their utility in clinical settings. Here, we assessed whether the measurement of serum IFN-α or selected IFN-induced cytokines accurately mirrors IFN-induced gene expression in ANA + individuals and investigated their utility as biomarkers of clinical progression., Methods: A total of 280 subjects were studied, including 50 ANA - healthy controls, 160 ANA + individuals without a SARD diagnosis (96 asymptomatic, 64 with undifferentiated connective tissue disease), and 70 SARD patients. IFN-induced gene expression was measured by nanoString and cytokine levels by ELISA or Simoa. ANA + individuals lacking a SARD diagnosis who had the new onset of SARD criteria over the subsequent 2 years were defined as progressors., Results: Measurement of IFN-α levels by high-sensitivity ELISA or Simoa correlated much better with IFN-induced gene expression than measurement of CXCL-10 or Galectin-9 levels. Despite this, high CXCL-10 and Galectin-9 levels were better predictors of subsequent progression in ANA + individuals than measures of IFN-α or IFN-induced gene expression with the optimal combination of predictive cytokines (CXCL-10 and IFN-α as measured by ELISA), resulting in a specificity and positive predictive value of 100%., Conclusion: Easily performed ELISA assays for CXCL-10 and IFN-α can be used to predict ANA + individuals at high risk of imminent symptomatic progression., (© 2023. The Author(s).)

Quality improvement is an emerging field, that applies principles of improvement science and utilizes measurement methods with the aim of improving patient care. Systemic sclerosis (SSc) is a systemic autoimmune rheumatic disease associated with increased healthcare burden, cost, morbidity, and mortality. Gaps in delivering care to patients with SSc have been consistently observed. In this article, we introduce the discipline of quality improvement and its use of quality measures. We summarize and comparatively evaluate three sets of quality measures that have been proposed to evaluate the quality of care of patients with SSc. Finally, we highlight the areas of unmet needs and indicate future directions for quality improvement and quality measures in SSc.

Background: Hepatitis C is a diverse illness that causes significant death and morbidity. The hepatitis C virus infects hundreds of millions of individuals globally (HCV). More than 80% of those infected develop chronic infection; the remaining 10-20% recovers spontaneously through natural immunity. Acute hepatitis is only icteric in 20% of individuals and is seldom severe., Methods: A pilot study was conducted at INOR hospital Abbottabad. Eleven hepatitis C positive and 10 hepatitis C negative participants were included in the study., Results: A significant difference correlation was found between viral load and SWE quantification for fibrosis stage in Kilo-Pascal, r=0.904 (p-value=0.000

Background: For the treatment of hypothyroidism, patients are usually placed on lifelong levothyroxine replacement therapy. Achieving clinical and biochemical euthyroid status is sometimes difficult because of several factors, including poor compliance or poor absorption of levothyroxine in the gut mucosa., Case Presentation: We present the case of a 45-year-old South Asian female with hypothyroidism on lifelong levothyroxine replacement. However, on her multiple follow-up visits over the past 2 years, it was noted that her thyrotropin level was never controlled and was not in range. A thorough history was unyielding in terms of compliance regarding levothyroxine medication and use of over-the-counter pills or mineral supplements that may interfere with the absorption of levothyroxine. Hence, we performed levothyroxine absorption test to rule out any malabsorption as well as document pseudo-malabsorption favoring drug nonadherence. Levothyroxine absorption test resulted in more than 56% absorption of levothyroxine; therefore, the patient was put on weekly directly observed treatment strategy resulting in normalization of thyrotropin levels on successive follow-ups., Conclusion: Directly observed treatment to replace levothyroxine once a week can be used as an alternative by health care professionals in patients in whom compliance to daily levothyroxine is the hidden cause of persistently raised thyrotropin. This strategy can reduce undue health burden on the patient and improve adherence to self-medication under confident supervision of the treating physician., (© 2023. The Author(s).)

An intraverbal assessment was administered to older adults with aphasia, using a hierarchy of questions that required increasingly complex verbal discriminative stimulus control. Five categories of errors were defined and analyzed for putative stimulus control, with the aim to identify requisite assessment components leading to more efficient and effective treatments. Evocative control over intraverbal error responses was evident throughout the database, as shown by commonalities within four distinct categories of errors; a fifth category, representing a narrow majority of errors, was less clear in terms of functional control over responses. Generally, questions requiring increasingly complex intraverbal stimulus control resulted in weaker verbal performance for those with aphasia. A new 9-point intraverbal assessment model is proposed, based on Skinner's functional analysis of verbal behavior. The study underscores that loss or disruption of a formerly sophisticated language repertoire presents differently than the fledgling language skills and errors of new learners, such as typically developing children and those with autism or developmental disabilities. Thus, we would do well to consider that rehabilitation may require a different approach to intervention than habilitation. We offer several thematic topics for future research in this area., Competing Interests: Conflicts of interestThe authors have no conflicts of interest to declare., (© Association for Behavior Analysis International 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

High-risk-human papillomavirus (HR-HPV)-induced cervical cancer is the second most common cause of death among females worldwide. HPV16 is the most prevalent HR-HPV infection worldwide. This study found the genotypic distribution of HR-HPV in the local population and investigated the sequence variations among the E6 and E7 oncogenes of the local HPV16 genotype to the E6 and E7 oncogenes of the foreign HPV16 genotypes and constructed a phylogenetic relationship based on nucleotide sequence comparison among the variants identified in our study along with previously reported isolates that were obtained from different regions of the world. The samples were collected from patients with cervical cancer. Genomic DNA was extracted, and HR-HPV genotypes were determined using real-time PCR. The HPV16 E6 and E7 genes were amplified and sequenced. A HPV16 phylogenetic tree was constructed using the maximum likelihood method with MEGA 7. HPV16 was the most prevalent human papillomavirus (HPV) type identified in the present study. HPV16 isolates belonged to the A1 sublineage of the European branch. Twenty-one nucleotide sequences were included in this analysis. The first, second, and third codon positions are also included. The final dataset included 776 positions., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Digital health interventions (DHIs) for the prevention and management of cardiometabolic diseases have become increasingly common. However, there is limited evidence for the suitability of these approaches in minority ethnic populations, who are at an increased risk of these diseases., Objective: This study aimed to investigate the use of DHIs for cardiovascular disease and type 2 diabetes among minority ethnic populations in countries with a majority of White, English-speaking populations, focusing on people who identified as South Asian, Black, or African American., Methods: A realist methodology framework was followed. A literature search was conducted to develop context-mechanism-outcome configurations, including the contexts in which DHIs work for the target minority ethnic groups, mechanisms that these contexts trigger, and resulting health outcomes. After systematic searches, a qualitative analysis of the included studies was conducted using deductive and inductive coding., Results: A total of 15 studies on the uptake of DHIs for cardiovascular disease or diabetes were identified, of which 13 (87%) focused on people with an African-American background. The review found evidence supporting the use of DHIs in minority ethnic populations when specific factors are considered in implementation and design, including patients' beliefs, health needs, education and literacy levels, material circumstances, culture, social networks, and wider community and the supporting health care systems., Conclusions: Our context-mechanism-outcome configurations provide a useful guide for the future development of DHIs targeted at South Asian and Black minority ethnic populations, with specific recommendations for improving cultural competency and promoting accessibility and inclusivity of design., (©Aumeya Goswami, Lydia Poole, Zareen Thorlu-Bangura, Nushrat Khan, Wasim Hanif, Kamlesh Khunti, Paramjit Gill, Madiha Sajid, Ann Blandford, Fiona Stevenson, Amitava Banerjee, Mel Ramasawmy. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.01.2023.)

Aromatic polyamides are well-known as high-performance materials due to their outstanding properties making them useful in a wide range of applications. However, their limited solubility in common organic solvents restricts their processability and becomes a hurdle in their applicability. This study is focused on the synthesis of processable ferrocene-based terpolyamides and their polydimethylsiloxane (PDMS)-containing block copolymers, using low-temperature solution polycondensation methodology. All the synthesized materials were structurally characterized using FTIR and 1 H NMR spectroscopic techniques. The ferrocene-based terpolymers and block copolymers were soluble in common organic solvents, while the organic analogs were found only soluble in sulfuric acid. WXRD analysis showed the amorphous nature of the materials, while the SEM analysis exposed the modified surface of the ferrocene-based block copolymers. The structure-property relationship of the materials was further elucidated by their water absorption and thermal behavior. These materials showed low to no water absorption along with their high limiting oxygen index (LOI) values depicting their good flame-retardant behavior. DFT studies also supported the role of various monomers in the polycondensation reaction where the electron pair donation from HOMO of diamine monomer to the LUMO of acyl chloride was predicted, along with the calculation of various other parameters of the representative terpolymers and block copolymers.

There is an increasing body of literature suggesting a relationship between environmental factors and the development of systemic sclerosis (SSc). These include occupational exposures, chemical materials, medications, alterations in the microbiome, and dysbiosis. Environmental exposures may impact epigenetic regulation thereby triggering an aberrant immune response resulting in the clinical and serologic phenotype that we diagnose as SSc. Screening and studying putative triggers will not only improve our understanding of the pathogenesis of SSc but also inform the institution for protective measures., Competing Interests: Disclosures Dr. Johnson is supported by the Gurmej Kaur Dhanda Scleroderma Research Award, Scleroderma Association of British Columbia., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Meaningful Equity, Diversity, and Inclusion (EDI) efforts may be stymied by concerns about whether proposed initiatives are performative or tokenistic. The purpose of this project was to analyze discussions by the Research in Medical Education (RIME) Program Planning committee about how best to recognize and support underrepresented in medicine (URiM) researchers in medical education to generate lessons learned that might inform local, national, and international actions to implement meaningful EDI initiatives. Ten RIME Program Planning Committee members and administrative staff participated in a focus group held virtually in August 2021. Focus group questions elicited opinions about "if and how" to establish a URiM research award. The focus group was recorded, transcribed, and thematically analyzed. Recognition of privilege, including who has it and who doesn't, underpinned the focus group discussion, which revolved around 2 themes: (1) tensions between optics and semantics, and (2) potential unintended consequences of trying to level the medical education playing field. The overarching storyline threaded throughout the focus group discussion was intentionality. Focus group participants sought to avoid performativity by creating an award that would be meaningful to recipients and to career gatekeepers such as department chairs and promotion and tenure committees. Ultimately, participants decided to create an award that focused on exemplary Equity, Diversity, and Inclusion (EDI) scholarship, which was eventually named the "RIME URiM Research Award." Difficult but productive conversations about EDI initiatives are necessary to advance underrepresented in medicine (URiM) scholarship. This transparent commentary may trigger further critical conversations., (Copyright © 2022 by the Association of American Medical Colleges.)

Acute Pancreatitis (AP) is the inflammation of the pancreas that can be fatal or lead to further complications based on the severity of the attack. Early detection of AP disease can help save lives by providing utmost care, rigorous treatment, and better resources. In this era of data and technology, instead of relying on manual scoring systems, scientists are employing advanced machine learning and data mining models for the early detection of patients with high chances of mortality. The current work on AP mortality prediction is negligible, and the few studies that exist have many shortcomings and are impractical for clinical deployment. In this research work, we tried to overcome the existing issues. One main issue is the lack of high-quality public datasets for AP, which are crucial for effectively training ML models. The available datasets are small in size, have many missing values, and suffer from high class imbalance. We augmented three public datasets, MIMIC-III, MIMIC-IV, and eICU, to obtain a larger dataset, and experiments proved that augmented data trained classifiers better than original small datasets. Moreover, we employed emerging advanced techniques to handle underlying issues in data. The results showed that iterative imputer is best for filling missing values in AP data. It beats not only the basic techniques but also the Knn-based imputation. Class imbalance is first addressed using data downsampling; apparently, it gave decent results on small test sets. However, we conducted numerous experiments on large test sets to prove that downsampling in the case of AP produced misleading and poor results. Next, we applied various techniques to upsample data in two different class splits, a 50 to 50 and a 70 to 30 majority-minority class split. Four different tabular generative adversarial networks, CTGAN, TGAN, CopulaGAN, and CTAB, and a variational autoencoder, TVAE, were deployed for synthetic data generation. SMOTE was also utilized for data upsampling. The computational results showed that the Random Forest (RF) classifier outperformed all other classifiers on a 50 to 50 class split data generated by CTGAN, with 0.702 F β and 0.833 recall. Results produced by RF on the TVAE dataset were also comparable, with 0.698 F β . In the case of SMOTE-based upsampling, DNN performed best with a 0.671 F β score., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The main goal of stroke rehabilitation is to improve the health-related quality of life (HRQoL). In developed countries, several studies evaluating the HRQoL among stroke survivors have been conducted. In India, HRQoL related to stroke as an important health care issue has not received sufficient attention. The study was conducted to encourage the professionals to use stroke-specific HRQoL scales in clinical practice as one of the measures of stroke outcome., Objectives: To study the correlation between activities of daily living (ADLs) and HRQoL at 90 days following an acute stroke., Methods: In this prospective study, functional independence of patients admitted with stroke were measured using Barthel Index (BI). At 90 days post-stroke patients were assessed using two questionnaires., Results: Significant improvement in BI total and domains scores at 90 days (p < .001) were seen. At follow-up, Stroke Specific Quality of Life Scale-12 (SS-QoL-12) score for 59 patients was 48 (high QoL). Individuals scored lowest for psychosocial subscale of HRQoL compared to physical subscale. All items and the total score of the BI showed a significant positive partial correlation (p< .001) with the HRQoL total score. The self-care domain of BI showed the highest correlation with QoL total score at 0.88., Conclusions: Patient dependent in ADL constantly scored less in all QoL domains. The psychosocial QoL was found to be most affected even in the presence of complete functional independence paving way for further studies on factors that impact psychosocial QoL of stroke survivors., Competing Interests: Declaration of Competing Interest The author declares that there is no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A study was conducted to determine the prevalence and drug resistance of Escherichia coli present in urinary tract infected patients and hospital drinking water. A total of eighty urine samples from clinically suspected patients and thirty tap water samples from hospital vicinity were collected and analyzed for the presence of E. coli . The isolates were preliminary identified based on morphological characteristics, biochemical test and further confirmed by polymerase chain reaction (PCR) using uidA primer. Isolates were subjected to antibiogram studies and analyzed for the presence of drug resistance ( ESBL blaCTX-M-15 , tetA , and TMP-SMX dfrA1 ) and pathogenicity associated pyelonephritis-associated pili ( PAP ) and Heat-labile (LT) toxin genes. Urine samples 19/80 (23.75%) and water samples 8/30 (26.7%) were found contaminated with E. coli . It was found that 12/19 (63%) bacterial isolates were extended spectrum beta-lactamase (ESBL) producers in clinical and 6/8 (75%) in water isolates whereas tetracycline resistance in clinical and water isolates was 11/19 (58%) and 6/8 (75%), respectively. The trimethoprim resistance gene was confirmed in 12/19 (63%) in clinical and 2/8 (25%) in water isolates. All the clinical and water isolates were found carrying pili PAP gene. It was concluded that the presence of drug resistant and pathogenic E. coli in clinical and water samples is extremely alarming for public health due to cross contamination and bacterial transfer from clinical samples to water and vice versa., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Ali Akbar et al.)

There is an increasing interest in the use of beneficial microorganisms as alternatives to chemically synthesized or plant-derived molecules to produce therapeutic agents. Bacterial endophytes are plant-associated microorganisms that can colonize different parts of living plants without causing any diseases. Diverse endophytic bacteria possess the ability to synthesize a wide range of secondary metabolites with unique chemical structures that have been exploited for their anti-microbial, antiviral, anti-cancer, and anti-inflammatory properties. Additionally, production of these bioactive compounds can also benefit the host plant as they may play a significant role in a plant's interaction with the environment for adaptation and defense. As a result of their significant impact as curative compounds or as precursors to produce new drugs, the biotechnological possibilities of secondary metabolites derived from endophytic bacteria are immense.

Propolis is a well-known resinous natural substance collected by honeybees ( Apis mellifera L.) from plants exudations. Variations in chemical composition of propolis are due to different sources from which it is collected and change in climate and geographical location. In this study, different propolis samples were collected from different regions of Balochistan and examined for its chemical composition, total phenolics and total flavonoid contents, and antioxidant potential by using DPPH radical scavenging assay and antimicrobial activity. Bioactive components analysis revealed the presence of steroids, carbohydrates, flavonoids, coumarins, cardiac glycosides, quinones, anthraquinones, terpenoids, tannins, and phlobatannins at different levels. The total phenolics contents were ranged from 2.9343 ± 1.247 to 6.0216 ± 2.873 mg GAE g -1 , and flavonoid contents were found to be 0.1546 ± 0.087 to 0.6586 ± 0.329 mg QE g -1, respectively. The antioxidant ability of each extract was analyzed by their concentration having 50% inhibition ( IC 50 ). The propolis sample P3 possessed lower IC 50 27.07 ± 0.73 mg mL -1 with higher % inhibition of DPPH radical, and P8 showed lower % inhibition by having IC 50 84.43 ± 2.07 mg mL -1 . The antibacterial activity of all samples was analyzed against a wide group of bacteria including Escherichia coli , Staphylococcus aureus , Pseudomonas aeruginosa , and Klebsiella pneumonia and propolis extract (P4) was highly active against Klebsiella pneumoniae with the maximum diameter of zone of inhibition 20.33 ± 1.52 mm, and propolis extract (P3) showed maximum zone of inhibition against Escherichia coli 19.06 ± 1.90, while propolis extract (P2) was found less active with minimum diameter of zone of inhibition 7.46 ± 1.50 mm. The antifungal activity of extract was considered as active against the fungal species. Propolis extract (P3) showed 82% of zone of inhibition against Aspergillus Niger , and propolis extract (P1) was highly active against Aspergillus parasiticus with 80% of zone of inhibition. By comparing the vibration frequencies in wave numbers of the sample spectrograph acquired from an FTIR spectrophotometer, the functional groups present in the extracts were identified. The presence of seven elements (Fe, Zn, Mn, Ni, Pb, Cd, and Cr) was analyzed through atomic absorption spectrophotometer. The obtained concentrations were within the permissible ranges established by the World Health Organization. The GC-MS analysis revealed the presence of 80 different compounds belonged to different classes. The obtained results confirmed the imperative potential of propolis which can be used in various biological applications., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Ali Akbar et al.)

The use of perovskites in photovoltaic and related industries has achieved tremendous success over the last decade. However, there are still obstacles to overcome in terms of boosting their performance and resolving stability issues for future commercialization. The introduction of a new 2D material of halide perovskites is now the key advancement in boosting the solar energy conversion efficiency. The implication of a new 2D material (MXene) in perovskite solar cells has been initiated since its first report in 2018, showing excellent transparency, electrical conductivity, carrier mobility, superior mechanical strength, and tunable work function. Based on distinctive features at the hetero-interface, halide perovskite and MXene heterostructures (HPs/Mx) have recently exhibited exceptional improvements in both the performance and stability of perovskite solar cells. Furthermore, the wide families of HPs and MXene materials allow playing with the composition and functionalities of HP/Mx interfaces by applying rational designing and alterations. In this review a comprehensive study of implementing MXenes in perovskite solar cells is presented. First, the implementation of MXenes in perovskites as an additive, and then in charge extraction layers (HTL/ETL), is described in detail. It is worth noting that still only Ti 3 C 2 T x , Nb 2 CT x ,V 2 CT x MXene is being incorporated into perovskite photovoltaics. Finally, the present obstacles in the use of MXenes in PSCS are discussed, along with the future research potential. This review is expected to provide a complete and in-depth description of the current state of research and to open up new opportunities for the study of other MXenes in PSCs.

Eremophilanes are a large group of "sesquiterpenes" produced by plants and fungi, with more than 180 compounds being known in fungi alone. Many of these compounds are phytotoxic, antimicrobial, anticancer and immunomodulators, and hence are of great economic values. Acremeremophilanes A to O have earlier been reported in a marine isolate of Acremonium sp. We report here the presence of Acremeremophilane I, G, K, N, and O, in a plant beneficial fungus Trichoderma virens , in a strain-specific manner. We also describe a novel, P strain-specific polyketide synthase (PKS) gene cluster in T. virens . This gene cluster, designated amm cluster, is absent in the genome of a Q strain of T. virens , and in other Trichoderma spp.; instead, a near identical cluster is present in the genome of the toxic mold Stachybotrys chartarum. Using gene knockout, we provide evidence that acremeremophilanes are biosynthesized via a polyketide route, and not via the mevalonate/terpene synthesis route as believed. We propose here that the 10-carbon skeleton is a product of polyketide synthase, to which a five-carbon isoprene unit is added by a prenyl transferase (PT), a gene for which is present next to the PKS gene in the genome. Based on this evidence, we propose that at least some of the eremophilanes classified in literature as sesquiterpenes (catalyzed by terpene cyclase) are actually meroterpenes (catalyzed by PKSs and PTs), and that the core moiety is not a sesquiterpene, but a hybrid polyketide/isoprene unit. IMPORTANCE The article contradicts the established fact that acremeremophilane metabolites produced by fungi are sesquiterpenes; instead, our findings suggest that at least some of these well-studied metabolites are of polyketide origin. Acremeremophilane metabolites are of medicinal significance, and the present findings have implications for the metabolic engineering of these metabolites and also their overproduction in microbial cell factories.

Background: Digital health interventions have become increasingly common across health care, both before and during the COVID-19 pandemic. Health inequalities, particularly with respect to ethnicity, may not be considered in frameworks that address the implementation of digital health interventions. We considered frameworks to include any models, theories, or taxonomies that describe or predict implementation, uptake, and use of digital health interventions., Objective: We aimed to assess how health inequalities are addressed in frameworks relevant to the implementation, uptake, and use of digital health interventions; health and ethnic inequalities; and interventions for cardiometabolic disease., Methods: SCOPUS, PubMed, EMBASE, Google Scholar, and gray literature were searched to identify papers on frameworks relevant to the implementation, uptake, and use of digital health interventions; ethnically or culturally diverse populations and health inequalities; and interventions for cardiometabolic disease. We assessed the extent to which frameworks address health inequalities, specifically ethnic inequalities; explored how they were addressed; and developed recommendations for good practice., Results: Of 58 relevant papers, 22 (38%) included frameworks that referred to health inequalities. Inequalities were conceptualized as society-level, system-level, intervention-level, and individual. Only 5 frameworks considered all levels. Three frameworks considered how digital health interventions might interact with or exacerbate existing health inequalities, and 3 considered the process of health technology implementation, uptake, and use and suggested opportunities to improve equity in digital health. When ethnicity was considered, it was often within the broader concepts of social determinants of health. Only 3 frameworks explicitly addressed ethnicity: one focused on culturally tailoring digital health interventions, and 2 were applied to management of cardiometabolic disease., Conclusions: Existing frameworks evaluate implementation, uptake, and use of digital health interventions, but to consider factors related to ethnicity, it is necessary to look across frameworks. We have developed a visual guide of the key constructs across the 4 potential levels of action for digital health inequalities, which can be used to support future research and inform digital health policies., (©Mel Ramasawmy, Lydia Poole, Zareen Thorlu-Bangura, Aneesha Chauhan, Mayur Murali, Parbir Jagpal, Mehar Bijral, Jai Prashar, Abigail G-Medhin, Elizabeth Murray, Fiona Stevenson, Ann Blandford, Henry W W Potts, Kamlesh Khunti, Wasim Hanif, Paramjit Gill, Madiha Sajid, Kiran Patel, Harpreet Sood, Neeraj Bhala, Shivali Modha, Manoj Mistry, Vinod Patel, Sarah N Ali, Aftab Ala, Amitava Banerjee. Originally published in JMIR Cardio (https://cardio.jmir.org), 11.08.2022.)

Intersectionality theory examines how matrices of power and interlocking structures of oppression shape and influence people's multiple identities. It reminds us that people's lives cannot be explained by taking into account single categories, such as gender, race, sexuality, or socio-economic status. Rather, human lives are multi-dimensional and complex, and people's lived realities are shaped by different factors and social dynamics operating together. Therefore, when someone occupies multiple marginalized intersections, their individual-level experiences reflect social and structural systems of power, privilege, and inequality. And yet, knowing that people occupy different social locations that afford them unique experiences is not the same as knowing how to analyze data in an intersectional way. Intersectional analyses are rigorous, and require the use of theory at multiple levels to see theoretical connections that are often only implicit.In this paper, we ask "How does one actually do intersectional research and what role does theory play in this process?" In an effort to make intersectionality theory more accessible to health professions education research, this article describes the simpler version of intersectional analyses followed by the more complex version representing how it was originally intended to be used; a means to fight for social justice. Using pilot data collected on first-generation medical students' professional identity experiences, we demonstrate the thinking and engagement with theory that would be needed to do an intersectional analysis. Along the way, we describe some of the challenges researchers may find in using intersectionality in their own work. By re-situating the theory within its original roots of Black feminist thought, we hope other health professions education (HPE) researchers consider using intersectionality in their own analyses., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Berberis baluchistanica Ahrendt is a medicinal plant potentially known for the treatment of different diseases. The bioactive, antioxidant, nutritional components, and antimicrobial properties of crude ethanolic root extract of Berberis baluchistanica were evaluated in this study. The extract was analyzed for total phenolic, flavonoid, DPPH (2, 2-diphenyl-1-picryl-hydrazyl) scavenging ability, FRAP (ferric reducing antioxidant power), nutritional, and antimicrobial potentials. The alkaloids, tannins, cardiac glycosides, anthraquinones, coumarin, saponins, phenolics, flavonoids, steroids, and terpenoids were confirmed. The extract possessed DPPH radical inhibition with the IC 50 of 1.125 mg/mL and FRAP % reduction activity with IC 50 (0.912 mg/mL). Total phenolic 19.897 ± 4.8141 mg GAE/g and flavonoid 12.9876 ± 0.8388 mg QE/g contents were confirmed in the root. The extracts exhibit good antibacterial activity against a broad spectrum of food borne pathogens Pseudomonas aeruginosa , Salmonella typhi , Klebsiella pneumoniae , Escherichia coli , and Staphylococcus aureus . The highest inhibitory activity was against Escherichia coli 23.30 ± 1.16 mm and lowest against Klebsiella pneumoniae 7 ± 0.01 mm. Furthermore, the presence of various phytochemical constituents (plant secondary metabolites) was also confirmed with gas chromatography and mass spectroscopy analysis. Results disclosed the occurrence of more than 70 compounds possessing various medicinal properties supporting the traditional uses of root of Berberis baluchistanica in various medical complications indigenously., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Zareen Gul et al.)

Background: Cotton production is adversely effected by drought stress. It is exposed to drought stress at various critical growth stages grown under a water scarcity environment. Roots are the sensors of plants; they detect osmotic stress under drought stress and play an important role in plant drought tolerance mechanisms. The seedling stage is very sensitive to drought stress, and it needed to explore the methods and plant characteristics that contribute to drought tolerance in cotton., Results: Initially, seedlings of 18 genotypes from three Gossypium species: G. hirsutum, G. barbadense, and G. arboreum, were evaluated for various seedling traits under control (NS) and drought stress (DS). Afterward, six genotypes, including two of each species, one tolerant and one susceptible, were identified based on the cumulative drought sensitivity response index (CDSRI). Finally, growth rates (GR) were examined for shoot and root growth parameters under control and DS in experimental hydroponic conditions. A significant variation of drought stress responses was observed across tested genotypes and species. CDSRI allowed here to identify the drought-sensitive and drought-resistant cultivar of each investigated species. Association among root and shoots growth traits disclosed influential effects of enduring the growth under DS. The traits including root length, volume, and root number were the best indicators with significantly higher differential responses in the tolerant genotypes. These root growth traits, coupled with the accumulation of photosynthates and proline, were also the key indicators of the resistance to drought stress., Conclusion: Tolerant genotypes have advanced growth rates and the capacity to cop with drought stress by encouraging characteristics, including root differential growth traits coupled with physiological traits such as chlorophyll and proline contents. Tolerant and elite genotypes of G. hirsutum were more tolerant of drought stress than obsolete genotypes of G. barbadense and G. arboreum. Identified genotypes have a strong genetic basis of drought tolerance, which can be used in cotton breeding programs., (© 2022. The Author(s).)

Objective: To evaluate improvement in nutrition support therapy after the implementation of nutritional protocols in critically ill surgical patients., Methods: The ambidirectional study was conducted at the surgical intensive care unit of Aga Khan University Hospital, Karachi, using an evidenced-based nutritional protocol. The pre-protocol retrospective data group A comprised patient records from July to September 2018, while the post-protocol prospective data group B related to the period between October and December 2018. Both data sets involved patients of either gender aged at least 18 years who needed admission to surgical intensive care unit and were unable to take oral nutrition for >2 days and remained under intensive care for up to seven days. Data was analysed using SPSS 21., Results: Of the 65 patients, 30(46.2%) were in group A; 21(70%) males and 9(30%) females with mean age 40±16.55 years (range: 18-80 years). The remaining 35(53.8%) were in group B; 27(77%) males and 8(23%) females with mean age 48.66±17.7 years (range: 18-86 years). Nutritional screening indicated that 16(53.3%) patients in group A and 35(100%) in group B were at the risk of developing malnutrition. Patients receiving enteral nutrition within 24 hours of admission increased from 7(23.35%) in group A to 17 (48.3%) in group B. Overall, the amount of enterally administered calories increased from mean 321057±2495 kcal (29.6%) in group A to mean 384585±2343 (92.6%) in group B. The amount of protein administered increased from mean 622.2±148.7 kcal (14.7%) in group A to mean 549±125.48 kcal (67.1%) in group B., Conclusions: Implementation of nutritional protocol resulted in improved delivery of nutritional support in thesurgical intensive care unit.

Systemic Autoimmune Rheumatic Diseases (SARDs) are characterized by the production of anti-nuclear antibodies (ANAs). ANAs are also seen in healthy individuals and can be detected years before disease onset in SARD. Both the immunological changes that promote development of clinical symptoms in SARD and those that prevent autoimmunity in asymptomatic ANA + individuals (ANA + NS) remain largely unexplored. To address this question, we used flow cytometry to examine peripheral blood immune populations in ANA + individuals, with and without SARD, including 20 individuals who subsequently demonstrated symptom progression. Several immune populations were expanded in ANA + individuals with and without SARD, as compared with ANA - healthy controls, particularly follicular and peripheral T helper, and antibody-producing B cell subsets. In ANA + NS individuals, there were significant increases in T regulatory subsets and TGF-ß1 that normalized in SARD patients, whereas in SARD patients there were increases in Th2 and Th17 helper cell levels as compared with ANA + NS individuals, resulting in a shift in the balance between inflammatory and regulatory T cell subsets. Patients with SARD also had increases in the proportion of pro-inflammatory innate immune cell populations, such as CD14 + myeloid dendritic cells, and intermediate and non-classical monocytes, as compared to ANA + NS individuals. When comparing ANA + individuals without SARD who progressed clinically over the subsequent 2 years with those who did not, we found that progressors had significantly increased T and B cell activation, as well as increased levels of LAG3 + T regulatory cells and TGF-ß1. Collectively, our findings suggest that active immunoregulation prevents clinical autoimmunity in ANA + NS and that this becomes impaired in patients who progress to SARD, resulting in an imbalance favoring inflammation., 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 © 2022 Gupta, Vanlieshout, Manion, Bonilla, Kim, Muñoz-Grajales, Nassar, Johnson, Hiraki, Ahmad, Touma, Bookman and Wither.)

The goal of this work was to synthesize new cerium oxide-based nano-additives to minimise emissions from spark ignition (SI) engines fueled with gasoline blends, such as carbon monoxide (CO), unburned hydrocarbons (HC) and oxides of nitrogen (NO x ). To investigate the effect of transition metal dopants on their respective catalytic oxidation activity, nano-sized CeO 2 catalysts co-doped with Mn, Fe, Cu and Ag ions were successfully produced by a simple hydrothermal technique. The synthesis of nano-catalysts with cubic fluorite geometry was confirmed by XRD data. The addition of transition metal ions to the CeO 2 lattice increased the concentration of structural defects like oxygen vacancies and Ce 3+ ions, which are advantageous for the catalytic oxidation reaction, as also supported by XAFS and RAMAN analysis. Further, nano-gasoline fuel emission parameters are measured and compared to straight gasoline fuel. The results demonstrated that harmful exhaust pollutants such as CO, HC and NO x were significantly reduced. The high surface area, better redox characteristics and presence of additional oxygen vacancy sites or Ce 3+ ions have been linked to the improved catalytic performance of the synthesized catalyst., Competing Interests: The authors of this manuscript declare that they have no known personal relationships or competing financial interests which can have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Medicinal plants have great importance to the consumer health, as beside beneficial compounds, plants can accumulate essential and nonessential metals from soil and surrounding environments, leading to consumer health risks. Assuming this, the present study is aimed at evaluating the elemental composition and daily dose standardization based on essential and nonessential trace element presence in of bark, leaves, and roots of Berberis baluchistanica Ahrendt, a common medicinal plant used as a folk medicine in the region. Atomic absorption and flame emission spectroscopy were performed to analyze the presence of essential and nonessential elements manganese (Mn), copper (Cu), lead (Pb), nickel (Ni), iron (Fe), sodium (Na), and potassium (K). Among the essential elements, K was present at high concentrations in the bark (8926.98 ± 0.32  μ g/g), leaves (7922.77 ± 0.42  μ g/g), and roots (6668.5 ± 0.96  μ g/g) of the plant. The estimated concentration of Na was higher in leaves (1782.56 ± 0.13  μ g/g), followed by roots (1089.5 ± 0.71  μ g/g) and bark (572.8 ± 0.62  μ g/g). The Fe concentration varied in the range of 394.7 ± 0.3  μ g/g in bark, 1298.3 ± 0.54  μ g/g in leaves, and 1208.9 ± 0.7  μ g/g in roots. The trace transition element Mn was highest in leaves (42.7 ± 0.99  μ g/g), followed by roots (33.5 ± 0.94  μ g/g) and bark (22 ± 1  μ g/g). The Cu concentration was low, ranging from 20.1 ± 0.63 to 22.67 ± 0.7  μ g/g in leaves, bark, and roots. The obtained concentration of nonessential element Pb was relatively lower than the permissible range (10 mgL-1) established by the World Health Organization. The elemental concentrations in all parts were within the set limits for provisional tolerable daily maximum intake (PTDMI) and provisional tolerable weekly intake (PTWI), and the hazard quotient index (HQ) was below 1 for all toxic metals. The micro and macroelemental distribution and the overall medicinal potential of any medicinal plant can be correlated for dose risk estimation, which will be useful in providing knowledge regarding the contraindication associated with folk medicines. In the present study, based on the elemental composition, it was calculated that the daily safe dose for Berberis baluchistanica is approximately 2-5 g/day of raw powder for an adult, which must not be exceeded to this safe range., Competing Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2022 Zareen Gul et al.)

Berberis baluchistanica Ahrendt is a medicinal plant known to have potential for the treatment of various diseases. In the present study, the ethanolic extracts of the bark, leaves, and roots of B. baluchistanica plant were evaluated for in vitro antimicrobial, anti-leishmanial, anticancer, and anti-inflammatory activities. The antibacterial and antifungal activities were determined by agar mix and agar well diffusion method. All extracts showed potential activity against the target bacteria ( Bacillus subtilis , Bacillus licheniformis , Escherichia coli , Klebsiella pneumoniae , Pseudomonas aeruginosa , Rhodococcus erythropolis , Salmonella typhi , and Staphylococcus aureus ) and fungal strains ( Aspergillus flavus , Aspergillus niger , and Mucor mucedo ). S. aureus proved to be the most sensitive strain for each extract, with a maximum zone of inhibition for bark at 23 ± 0.12 mm, for leaves at 22 ± 0.36 mm, and for root extracts at 20.21 ± 0.06 mm). The minimum inhibitory concentration values of B. baluchistanica bark, leaves, and roots for different target bacterial strains ranged from 1.56 to 25 mg ml -1 , and the minimum bactericidal concentrations were in the range of 3.12 to 25 mg ml -1 , respectively. The root extract possessed potent antifungal activity against A. flavus with 83% of growth inhibition, A. niger with 80%, and M. mucedo with 73%. The bark extract was found active against M. mucedo with 86% of inhibition, followed by 70% against A. flavus and 60% against A. niger. The leaf extract showed a significant response by 83% inhibition against M. mucedo , followed by A. flavus and A. niger with 73 and 72% inhibition, respectively. In an anti-leishmanial bioassay, the inhibitory concentration (IC 50 ) was observed for each extract against Leishmania major . The bark showed good activity (IC 50 = 4.95 ± 0.36 mg/ml), followed by the roots (IC 50 = 7.07 ± 0.18 mg/ml) and the leaves (IC 50 = 8.25 ± 0.29 mg/ml). An evaluation of anticancer activity was done by using MTT cell assay against HeLa cell line. Upon comparing the values of each extract to the standard, it was revealed that the ethanolic bark extract showed the highest anticancer activity with IC 50 = (12 ± 0.15 μg/ml), followed by the roots (14 ± 0.15 μg/ml) and the leaves (17 ± 0.21 μg/ml), respectively. The anti-inflammatory assay was undertaken by the inhibition of albumin denaturation activity, proteinase inhibitory activity, and heat-induced hemolysis activity. The IC 50 value for protein denaturation of the bark was IC 50 = 0.64 ± 0.25 mg/ml, followed by the roots (0.67 ± 0.21 mg/ml) and the leaves (0.73 ± 0.13 mg/ml). The proteinase inhibitory activity of the bark extract was IC 50 = 0.55 ± 0.12 mg/ml, followed by the leaves (0.62 ± 0.23 mg/ml) and the roots (0.69 ± 0.15 mg/ml), respectively. For heat-induced hemolysis assay, the bark showed the lowest IC 50 value (0.48 ± 0.15 mg/ml) compared to the leaves (0.52 ± 0.35 mg/ml) and the roots (0.58 ± 0.05 mg/ml) of the plant. All analyzed parts of the B. baluchistanica plant showed significant biological activities which make the plant medicinally important and a good candidate for the isolation of antimicrobial, inflammatory, and anticancer compounds. Further studies may lead us to determine the active compounds responsible for the biological activities of the plant extracts., 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 © 2022 Gul, Akbar and Leghari.)

Objectives: The dosage of levothyroxine (LT4) during pregnancy differs among different ethnic groups worldwide. These differences are due to variations in geographical iodine distribution, autoimmunity, and variations in thyrotropin (TSH) targets for pregnancy. To the best of our knowledge, we report the levothyroxine dosage prescribed during pregnancy in hypothyroid women, for the first time from Pakistan., Results: Levothyroxine dosage of 280 hypothyroid women during pregnancy were reviewed. The median LT4 dosages prescribed before conception was 85.7 mcg per day which increased by 14.3 mcg per day in the first trimester (P 0.001). A significant difference in dosage was observed between controlled and uncontrolled TSH groups in the first trimester (P 0.05). Lower LT4 dosage was prescribed for subclinical hypothyroid women as compared to overt hypothyroid cases, whereas dosages did not differ according to autoimmune status in the latter part of gestation., (© 2022. The Author(s).)

Objective: We investigated the autoantibody (autoAb) profiles in ANA+ individuals lacking systemic autoimmune rheumatic disease (SARD) and early SARD patients to determine the key differences between these groups and identify factors that are associated with an increased risk of symptomatic progression within the next 2 years in ANA+ individuals., Methods: Using custom antigen (Ag) microarrays, 144 IgM and IgG autoAbs were surveyed in 84 asymptomatic and 123 symptomatic (48 UCTD and 75 SARD patients) ANA+ individuals. AutoAbs were compared in ANA+ individuals lacking a SARD diagnosis with ≥2 years follow-up (n = 52), including all those who demonstrated progression (n = 14) during this period, with changes over time assessed in a representative subset., Results: We show that ANA+ individuals have autoAb to many self-Ags that are not being captured by current screening techniques and very high levels of these autoAbs are predominantly restricted to early SARD patients, with SLE patients displaying reactivity to many more autoAgs than the other groups. In general, the symptoms that developed in progressors mirrored those seen in SARD patients with similar patterns of autoAbs. Only anti-Ro52 Abs were found to predict progression (positive predictive value 46%, negative predictive value 89%). Surprisingly, over 2 years of follow-up the levels of autoAbs remained remarkably stable regardless of whether individuals progressed or not., Conclusion: Our findings strongly argue that development of assays with an expanded set of auto-Ags and enhanced dynamic range would improve the diagnostic and prognostic ability of autoAb testing., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The role of nanoparticle shape in the interaction and adsorption of organic molecules on the particle surface is an unexplored area. On the other hand, such knowledge is not only vital for a basic understanding of organic molecule interaction with nanoparticle surfaces but also essential for evaluating the cellular uptake of nanoparticles for living organisms. The current study investigates the role of silica nanoparticle shape in the interactions of phthalic acid organic molecules by using molecular dynamics simulations. Silica nanoparticles of two different geometries namely spheroid and cuboid with varying charge densities along with protonated and deprotonated phthalic acid molecules are studied. The adsorption characteristics of phthalic acid molecules on these nanoparticles have been analysed under different aquatic environments. The interactions of phthalic acid molecules, water molecules and ions were found to be different for spheroid and cubic shaped particles at pH values of 2-3, 7 and 9-10. The interaction of phthalic acid molecules with cubical silica nanoparticles is enhanced compared to the spherical shape particles. Such an enhanced interaction was seen when the silica surface is neutral, pH 2-3 and when the silica surface is charged at pH 7 and pH 9-10 in the presence of 0.5 M NaCl electrolyte. The cuboid-shaped silica also exhibited more hydrophilicity and less negative surface potential compared to spheroid shaped particles at pH 9-10. This is due to the enhanced condensation of Na + counter-ions at the cuboid nanoparticle solution interface as to the interface of spheroid particles, which is well in agreement with Manning's theory of counter-ion condensation. Simulation results presented in this study indicate that the shape of the silica nanoparticle has significant influence on the interaction of water molecules, counter-ions and organic molecules which consequently determine the adsorption behaviour of organic molecules on the nanoparticle surface.

Background: As medical education grapples with larger issues of race and racism, researchers will need new tools to capture society's complex issues. One promising approach is bricolage, a methodological and theoretical approach that allows researchers to bend analytical tools to meet their needs. Bricolage is both a metaphor and an activity to describe the cognitively creative process researchers engage in while conducting interdisciplinary and multidimensional research., Process: At the heart of bricolage is the researchers' engagement in critical hermeneutics, which at its basic level recognises that all objects under study are subject to larger social, political, and historical forces that constrain individuals. Researching with bricolage treats objects of inquiry as part of a historically situated complex system. As such, data are interpreted in ways that build conceptual bridges between individuals' concrete experiences and concepts acknowledging larger social, historical, economic, and political forces., Pearls: To engage in bricolage, researchers should begin by reading and comparing ideas across disciplines to expose disciplinary-specific assumptions, as well as learn about new theories, approaches and methods that might be utilised for a bricolage project. Researchers should also ask themselves philosophical questions to identify new readings or their data. And finally, researchers should experiment with analytical metaphors because they help to frame new relationships between seemingly unrelated theories, methods and concepts. As researchers engage in bricolage, they need to sidestep their training and over-reliance on research protocols and checklists and engage in a creative tinkering to interpret the world in new ways. In doing so, scholars will be able to push traditional research boundaries and generate critical dialogue to move the field forward., (© 2021 Association for the Study of Medical Education and John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

This study aims to focus on Pakistan's fertilizer industry and investigate the causal relationships among environmental consciousness (ECO), green creativity (GCR), green mindfulness (GMD), and energy efficiency (EE), which are all essential mechanisms as well as circumstances that control the situation in well-developed manners. This study consists of a sample regarding four hundred and four (404) employees from seven companies by using partial least squares (PLS) and structural equation modeling (SEM) approach. The results indicate that environmental consciousness significantly and positively affects employee energy efficiency directly and indirectly in the presence of green creativity as a mediator. Moreover, the moderating effect of green mindfulness persisted only in the association between energy efficiency and green creativity. In the appropriate literature, this empirical investigation is the first of its kind which does not only provide an organized way to examine the effects of environmental consciousness on energy efficiency but also recommend the most effective means for employees and associations to embrace the best policies. This study has important policy implications for promoting clean production, clean environment, and sustainable development for developed and developing economies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Synthesis of Cu-doped NiO composited with cellulose nanocrystals (CNC) was carried out by co-precipitation method. The aim of this study is to investigate the catalytic, antibacterial and molecular docking studies of prepared samples. XRD patterns confirmed rhombohedral structure of synthesized nanostructures with gradual increase in crystallite size with doping. The morphology as well as interlayer spacing was evaluated with HRTEM while functional groups presence in dopant-free and doped nanostructures was confirmed using FTIR spectra. Both CNC/NiO composite and Cu-doped CNC/NiO showed higher catalytic potential compared to dopant-free NiO, while Cu-doped CNC/NiO nanostructures exhibited significant potential for use in industrial dye degradation applications. Besides this, CNC/NiO composite showed good antibacterial activity against Escherichia coli (E. coli) bacteria and its bacterial activity increased with Cu doping. Furthermore, molecular docking predictions against dihydrofolate reductase and DNA gyrase enzyme confirmed interaction of NiO NPs, CNC/NiO and Cu-doped CNC/NiO inside active pockets and showed good agreement with in vitro bactericidal activity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The ever-changing global environment currently includes an increasing ambient temperature that can be a devastating stress for organisms. Plants, being sessile, are adversely affected by heat stress in their physiology, development, growth, and ultimately yield. Since little is known about the response of biochemical traits to high-temperature ambiance, we evaluated eight parental lines (five lines and three testers) and their 15 F 1 hybrids under normal and high-temperature stress to assess the impact of these conditions over 2 consecutive years. The research was performed under a triplicate randomized complete block design including a split-plot arrangement. Data were recorded for agronomic, biochemical, and fiber quality traits. Mean values of agronomic traits were significantly reduced under heat stress conditions, while hydrogen peroxide, peroxidase, total soluble protein, superoxide dismutase, catalase (CAT), carotenoids, and fiber strength displayed higher mean values under heat stress conditions. Under both conditions, high genetic advance and high heritability were observed for seed cotton yield (SCY), CAT, micronaire value, plant height, and chlorophyll-a and b content, indicating that an additive type of gene action controls these traits under both the conditions. For more insights into variation, Pearson correlation analysis and principal component analysis (PCA) were performed. Significant positive associations were observed among agronomic, biochemical, and fiber quality-related traits. The multivariate analyses involving hierarchical clustering and PCA classified the 23 experimental genotypes into four groups under normal and high-temperature stress conditions. Under both conditions, the F 1 hybrid genotype FB-SHAHEEN × JSQ WHITE GOLD followed by Ghuari-1, CCRI-24, Eagle-2 × FB-Falcon, Ghuari-1 × JSQ White Gold, and Eagle-2 exhibited better performance in response to high-temperature stress regarding the agronomic and fiber quality-related traits. The mentioned genotypes could be utilized in future cotton breeding programs to enhance heat tolerance and improve cotton yield and productivity through resistance to environmental stressors., 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 © 2022 Zafar, Jia, Shakeel, Sarfraz, Manan, Imran, Mo, Ali, Youlu, Razzaq, Iqbal and Ren.)

The study of A-genome Asian cotton as a potential fiber donor in Gossypium species may offer an enhanced understanding of complex genetics and novel players related to fiber quality traits. Assessment of individual fibers providing classified fiber quality information to the textile industry is Advanced Fiber Information System (AFIS) in the recent technological era. Keeping the scenario, a diverse collection of 215 Asiatic cotton accessions were evaluated across three agro-ecological zones of China. Genome-Wide Association Studies (GWAS) was performed to detect association signals related to 17 AFIS fiber quality traits grouped into four categories viz: NEPs, fiber length, maturity, and fineness. Significant correlations were found within as well as among different categories of various traits related to fiber quality. Fiber fineness has shown a strong correlation to all other categories, whereas these categories are shown interrelationships via fiber-fineness. A total of 7,429 SNPs were found in association with 17 investigated traits, of which 177 were selected as lead SNPs. In the vicinity of these lead SNPs, 56 differentially expressed genes in various tissues/development stages were identified as candidate genes. This compendium connecting trait-SNP-genes may allow further prioritization of genes in GWAS loci to enable mechanistic studies. These identified quantitative trait nucleotides (QTNs) may prove helpful in fiber quality improvement in Asian cotton through marker-assisted breeding as well as in reviving eroded genetic factors of G . hirsutum via introgression breeding., 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 © 2021 Iqbal, Tang, Sarfraz, Iqbal, Li, He, Jia, Sun, Pan, Xiaoli, Mahmood, Ahmad, Nazir, Chen, Wang, Pang, Wei and Du.)

Competing Interests: The authors declare no conflict of interest.

Trichoderma virens produces viridin/viridiol, heptelidic (koningic) acid, several volatile sesquiterpenes and gliotoxin (Q strains) or gliovirin (P strains). We earlier reported that deletion of the terpene cyclase vir4 and a glyceraldehyde-3-phosphate dehydrogenase (GAPDH, designated as vGPD) associated with the "vir" cluster abrogated the biosynthesis of several volatile sesquiterpene metabolites. Here we show that, the deletion of this GAPDH also impairs the biosynthesis of heptelidic acid (a non-volatile sesquiterpene), viridin (steroid) and gliovirin (non-ribosomal peptide), indicating regulation of non-volatile metabolite biosynthesis by this GAPDH that is associated with a secondary metabolism gene cluster. To gain further insights into the details of this novel form of regulation, we identified the terpene cyclase gene responsible for heptelidic acid biosynthesis (hereafter designated as has1) and prove that the expression of this gene is regulated by vGPD. Interestingly, deletion of has1 impaired biosynthesis of heptelidic acid (HA), viridin and gliovirin, but not of volatile sesquiterpenes. Deletion of the vir cluster associated terpene cyclase gene (vir4), located next to the vGPD gene, did not impair biosynthesis of HA, viridin or gliovirin. We thus unveil a novel circuitry of regulation of secondary metabolism where an HA-tolerant GAPDH isoform (vGPD) regulates HA biosynthesis through the transcriptional regulation of the HA-synthase gene (which is not part of the "vir" cluster). Interestingly, impairment of HA biosynthesis leads to the down-regulation of biosynthesis of other non-volatile secondary metabolites, but not of volatile secondary metabolites. We thus provide evidence that the "vir" cluster associated, HA-tolerant GAPDH in T. virens participates in the biosynthesis of volatile sesquiterpenes as a biosynthetic enzyme, and regulates the production of non-volatile metabolites via regulation of HA biosynthesis. The orthologue of the "vir" cluster in Aspergillus oryzae was earlier reported to synthesize HA by another group. Our study thus proves that the same gene cluster can code for unrelated metabolites in different species., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

A specific functionality in the adsorbent materials plays a significant role for the selective capture of heavy metals based on Pearson's Hard-Soft-Acid-Base (HSAB) concept. Herein, we introduced single and double amino- and thiol-functionalities into the UiO-66 framework, which acted as hard and soft base sites for heavy metal adsorption, respectively. The synthesized adsorbents (labelled as NH 2 -UiO-66, (NH 2 ) 2 -UiO-66, SH-UiO-66 and (SH) 2 -UiO-66) were applied for the selective removal of lead (Pb) ions from contaminated water. The removal efficiency of Pb was about 64, 85, 75 and 99% (pH = 6, T = 30 °C, sample dosage = 10 mg, Pb concentration = 100 mg L -1 ), respectively, based on available number of interacting sites in the respective adsorbent. To elaborate HSAB concept, the interacting sites of these functional groups towards Pb were explored by identifying their possible types of interactions in terms of soft acid-base affinity, coordinate and covalent bonding, chelation, π-π interactions and synergetic effect of bonding. Density functional theory (DFT) simulation was used to confirm these interactions and to help the better understanding of adsorption mechanism. Model fitting and characterization of Pb-sorbed adsorbents were also performed to reveal kinetics, order of adsorptive reaction, thermodynamics and adsorption mechanism. Moreover, the optimization of adsorptive removal was performed by controlled parameters including time, initial concentration, pH and temperature. The reusability and selectivity of these adsorbents along with recovery of Pb(II) were also assessed. This study presents the conceptual framework for the design of functional adsorbents in the removal of heavy metals using the HSAB principle as an intended guideline., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Maternal hypothyroidism has been reported to have concerns over neonatal outcomes, not only in the context of neurocognitive development but also in the short term as birth weight and neonatal jaundice., Patients and Methods: We conducted a cross-sectional retrospective study on 638 cases who delivered live births in the Aga Khan University Hospital after ethical approval. Data were collected on hypothyroid pregnant females who were diagnosed before conception or during their antenatal visits during the year 2008-2016. Neonatal outcomes were noted for birth weight, maturity, and neonatal jaundice, neonatal hypothyroidism, neonatal respiratory distress syndrome, sepsis, hypocalcaemia, congenital anomalies, need for intensive care admission, and neonatal death. Subgroup analysis was performed on the timing of diagnosis of maternal hypothyroidism. Data analysis was performed on Statistical Package for the Social Sciences version 20.0., Results: Neonatal jaundice was the most common neonatal outcome (37.6%) in our cohort of 662 live births. Nearly 15% required intensive care unit admission, however, neonatal death was very rare. The most common clinically significant congenital anomalies were cardiovascular defects, whereas Mongolian spots were the commonest congenital condition to report. There is a statistically significant association between low birth weight (OR 1.86, 95% CI 1.0-3.2, p ≤ 0.05) and congenital anomalies (OR 2.39, 95% CI 1.4-4.0, p ≤ 0.05) with women diagnosed with hypothyroidism before pregnancy., Conclusion: We report the neonatal outcomes and spectrum of congenital anomalies of hypothyroid pregnancies diagnosed before and during conception for the first time from the region of Pakistan.KEY MESSAGEOverall, none of the neonates of hypothyroid pregnancies developed congenital hypothyroidism.Cardiovascular defects in these neonates imply extensive screening and monitoring during pregnancy.Low birth weight and congenital anomalies are associated with the timings of diagnosis of hypothyroidism in pregnancy.

This study reports the polyphenol profile of helencha ( Enydra fluctuans Lour.), an underutilised, aquatic leafy vegetable, based on high resolution accurate mass analysis. The methanolic extract of helencha leaves was screened by ultra-high performance liquid chromatography with quadrupole time of flight mass spectrometry (LC-QToF-MS). An in-house developed database of phytochemical metabolites was referred for compound identifications. Based on the detection of the pseudomolecular ion and at least one molecule-specific fragment ion (each with < 5 ppm of mass error), 25 potentially-bioactive phenolic compounds were putatively identified. These included 6 flavonols, 4 phenolic acids, 3 lignans, 3 flavones and 1 each of flavanol, flavanone, dihydroflavonol, tetramethoxyflavone, isoflavonoid and methylated flavonol. In addition, 3 unclassified compounds are also reported. The helencha extract showed antibiofilm properties with a potent bacteriostatic activity against the clinical isolates of Pseudomonas aeruginosa , a human pathogenic bacteria. The complementary molecular docking studies indicated strong binding interactions of the identified compounds with the active site of LasR protein of P. aeruginosa. The in vitro and in silico study results would be useful to develop novel neutraceutical products based on helencha-extract and design new lead compounds to control the biofilm producing pathogenic microorganisms., Supplementary Information: The online version contains supplementary material available at (10.1007/s13197-021-04968-y)., Competing Interests: Conflicts of interestThe authors declare that they have no conflict of interest., (© Association of Food Scientists & Technologists (India) 2021.)

Defect engineering of metal organic frameworks offers potential prospects for tuning their features toward particular applications. Herein, two series of defective UiO-66 frameworks were synthesized via changing the concentration of the linker and synthetic temperature of the reaction. These defective materials showed a significant improvement in the capability of Pb(II) removal from wastewater. This strategy for defect engineering not only created additional active sites, more open framework, and enhanced porosity but also exposed more oxygen groups, which served as the adsorption sites to improve Pb(II) adsorption. A relationship among degree of defects, texture features, and performances for Pb(II) removal was successfully developed as a proof-of-concept, highlighting the importance of defect engineering in heavy metal remediation. To investigate the kinetic and adsorption isotherms, we performed adsorption experiments influenced by the time and concentration of the adsorbate, respectively. For the practicality of the materials, the most significant parameters such as pH, temperature, adsorbent concentration, selectivity, and recyclability as well as simulated natural surface water were also examined. This study provides a clue for the researchers to design other advanced defective materials for the enhancement of adsorption performance by tuning the defect engineering.

The drug delivery system (DDS) often causes toxicity, triggering undesired cellular injuries. Thus, developing supramolecules used as DDS with tunable self-assembly and nontoxic behavior is highly desired. To address this, we aimed to develop a tunable amphiphilic ABA-type triblock copolymer that is nontoxic to human blood cells but also capable of self-assembling, binding and releasing the clinically used drug dexamethasone. We synthesized an ABA-type amphiphilic triblock copolymer (P2L) by incorporating tetra(aniline) TANI as a hydrophobic and redox active segment along with monomethoxy end-capped polyethylene glycol (mPEG 2k ; M w  = 2000 g mol -1 ) as biocompatible, flexible and hydrophilic part. Cell cytotoxicity was measured in whole human blood in vitro and lung cancer cells. Polymer-drug interactions were investigated by UV-Vis spectroscopy and computational analysis. Our synthesized copolymer P2L exhibited tuned self-assembly behavior with and without external stimuli and showed no toxicity in human blood samples. Computational analysis showed that P2L can encapsulate the clinically used drug dexamethasone and that drug uptake or release can also be triggered under oxidation or low pH conditions. In conclusion, copolymer P2L is nontoxic to human blood cells with the potential to carry and release anticancer/anti-inflammatory drug dexamethasone. These findings may open up further investigations into implantable drug delivery systems/devices with precise drug administration and controlled release at specific locations., (© 2021. The Author(s).)

This year marks the 60th anniversary (1961-2021) of Research in Medical Education (RIME). Over the past 6 decades, RIME has selected medical education research to be presented each year at the Association of American Medical Colleges Annual Meeting: Learn Serve Lead and published in a supplement of Academic Medicine. In this article, the authors surveyed RIME chairs from the past 20 years to identify ways that RIME has advanced medical education research and to generate ideas for future directions. RIME chairs described advancements in the rigor and impact of RIME research and the timeliness of the topics, often serving as a driver for cutting-edge research. They highlighted RIME's role in promoting qualitative research, introducing new epistemologies, and encouraging networking as a means of career advancement. Going forward, RIME chairs suggested (1) strengthening collaborations with formal advanced MEd and PhD degree programs, (2) creating formal mentorship channels for junior and minority faculty, and (3) promoting research related to knowledge translation., (Copyright © 2021 by the Association of American Medical Colleges.)