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Abstract Irrigation rapidly expanded during the 20 t h century, affecting climate via water, energy, and biogeochemical changes. Previous assessments of these effects predominantly relied on a single Earth System Model, and therefore suffered from structural model uncertainties. Here we quantify the impacts of historical irrigation expansion on climate by analysing simulation results from six Earth system models participating in the Irrigation Model Intercomparison Project (IRRMIP). Results show that irrigation expansion causes a rapid increase in irrigation water withdrawal, which leads to less frequent 2-meter air temperature heat extremes across heavily irrigated areas (≥4 times less likely). However, due to the irrigation-induced increase in air humidity, the cooling effect of irrigation expansion on moist-heat stress is less pronounced or even reversed, depending on the heat stress metric. In summary, this study indicates that irrigation deployment is not an efficient adaptation measure to escalating human heat stress under climate change, calling for carefully dealing with the increased exposure of local people to moist-heat stress.

Urinary tract infection (UTI) is considered as one of the highly prevalent infections worldwide. Regarding its prevalence, UTI is more common in women. The outcome of the research is expected to predict the severity of the urinary tract infection. The study of prevalence and antibiotic susceptibility helps to provide data on the occurrence of uropathogens in different age groups and helps to treat the infection with effective antibiotics to prevent further progression of infection. The study has been carried out to identify and investigate the prevalence of uropathogens and to determine their antibiotic susceptibility potential. Overall, 713 urine samples were collected, MacConkey agar, Blood agar, CLED agar and Luria-Bertani agar were used for isolation of uropathogens by calibrated loop streak method and incubated at 37°C. Antibiotic susceptibility was carried out using the Kirby Disc diffusion method. A total of 665 showed positive bacteriuria. E. coli (37.3%) and K. pneumoniae (32.03%) were the most common uropathogens followed by E. fergusonii (17.9%), P. aeruginosa (8.4%), and A. baumannii (4.4%). The study found that above 70% of antibiotic susceptibility was observed in fluoroquinolones followed by imipenem, while all isolates showed high resistance to ampicillin. The organisms E. coli, E. fergusonii, and P. aeruginosa exhibited the least susceptibility (>50%) for third-generation cephalosporins. P. aeruginosa and A. baumannii showed no susceptibility to nitrofurantoin, whereas other isolates were least susceptible. The study concludes that K. pneumoniae and E. coli were highly prevalent within the study group and that fluoroquinolone and imipenem can be effective for treatment.

A diallel design was employed to assess the magnitude of heterosis, aiming to improve growth and yield of semi- indeterminate tomato by identifying the desirable cross- combinations. Five semi-indeterminate tomato genotypes (VRT13, EC15127, EC362941, EC521061 and EC521069) were crossed in diallel mating fashion during rainy (kharif) season of 2020. Crosses and the parents were examined for heterosis studies under naturally ventilated polyhouse during winter (rabi) season of 2020–21. The results revealed the presence of heterotic vigour in the growth and yield characteristics of the hybrids with significant differences among the traits studied. Hybrids from crosses EC15127 × EC362941 and VRT13 × EC362941 resulted negative heterosis over mid and better parent, respectively for days to first flowering indicating their earliness for flowering. VRT13 × EC15127 and EC15127 × EC362941 noticed heterosis over better and mid parent, respectively for fruit yield. Based on overall performance, the cross combinations EC15127 × EC362941, VRT13 × EC521061, VRT13 × EC15127, VRT13 × EC362941 and EC521069 × EC362941 were performed best over their parents for growth and yield parameters. Hence, these hybrids can be exploited directly or can be used further for development of improved commercial lines

Rationale & Objective: Complementary and alternative medicine (CAM) intake is widely prevalent in many parts of India. Heavy metals are known ingredients in some of these formulations. We studied the spectrum of glomerular diseases in patients using CAM. Study Design: Case series. Setting & Participants: Patients with proteinuria or unexplained acute kidney injury, who underwent a kidney biopsy between May 2021 and September 2022, and who provided a history of recent CAM intake were included in the study. For patients enrolled prospectively, blood and urine samples were analyzed using mass spectrometry for the presence of mercury, lead, arsenic and cadmium. The CAM formulation, when available, was analyzed using inductively coupled plasma-optical emission spectroscopy. Results: Twenty-eight patients were enrolled in the study, with a median duration of CAM intake of 4 months (interquartile range, 2-6 months). Heavy metal screening was performed in 17 patients, of whom 15 had elevated urine mercury levels, 10 had elevated blood mercury levels, and 1 had elevated blood and urine arsenic levels. Of the 6 CAM formulations that were analyzed, all had high levels of mercury. Kidney biopsy findings were membranous nephropathy (n = 19), minimal change disease (n = 8), and mesangial proliferative glomerulonephritis (n = 1). Of the 19 patients with membranous nephropathy, 14 were associated with neural epidermal growth factor-like protein 1 (NELL-1). With conservative management alone, 17 patients achieved complete remission. Limitations: Not all patients underwent blood and urine mercury testing, and only 6 patients provided the CAM samples for analysis. Furthermore, occupational and residential exposure to mercury could not be excluded. Conclusions: The most common kidney pathology noted in our study was membranous nephropathy, which was predominantly associated with neural epidermal growth factor-like protein 1. A significant proportion of the patients recovered completely after withdrawal of the offending agent and initiation of renin-angiotensin system blockade. Plain Language Summary: Complementary and alternative medicine (CAM) intake is widely prevalent in many parts of India, and heavy metals are known ingredients in some of these formulations. We describe the clinical spectrum of kidney disease, among patients who had recently ingested CAM. All patients underwent a kidney biopsy, and the most common finding was an entity called “NELL-1-associated membranous nephropathy,” which is known to be associated with heavy metal toxicity and CAM intake. Of 17 patients screened for such heavy metals, 15 had greater-than-permissible levels of mercury. Furthermore, 6 patients provided the CAM formulations that they had consumed for analysis: all contained high levels of mercury. Most such patients recovered following withdrawal of the offending CAM agent.

Antimicrobial resistance (AMR) is a global public health concern and needs to be monitored for control. In this study, synanthropic rodents trapped from humans and animal habitats in Puducherry, India, were screened as sentinels for bacterial pathogens of public health importance and antimicrobial resistance spillover. From the trapped rodents and shrews (n = 100) pathogens viz., Staphylococcus sp, E. coli and Salmonella sp were isolated from oropharyngeal and rectal swabs on Mannitol salt, Mac Conkey and Xylose lysine deoxycholate media respectively. The AMR genes in these isolates were screened by PCR. A total of 76, S. aureus and 19, Staphylococcus non aureus were isolated. E. coli was isolated in 89 samples and among the Salmonella sp (n = 59), 16, were S. enteritidis and 29, were S. typhimurium. A total of 46 MRSA isolates with mec A (n = 40) and mec C (n = 6) were detected. Also, 36.84% and 5.3% Staphylococcus non aureus isolates were tested to have mec A and mec C genes. AMR genes encoding ESBL [blaTEM in 21, blaSHV in 45 and blaCTX-M in 11] was tested positive in 77 E. coli isolates. Among, Salmonella isolates 44/45 were screened to have AMR genes [tet in 13, sul3 & sul4 in 20 and qnrA in 11]. Antibiotic sensitivity test confirmed the antimicrobial resistance. Isolation of pathogens of public health importance and demonstration of genetic elements conferring antimicrobial resistance in the synanthropic rodents confirms that they act as reservoirs and appropriate sentinels to monitor AMR spillover in the environment.

β-thalassemia/HbE results from mutations in the β-globin locus that impede the production of functional adult hemoglobin. Base editors (BEs) could facilitate the correction of the point mutations with minimal or no indel creation, but its efficiency and bystander editing for the correction of β-thalassemia mutations in coding and non-coding regions remains unexplored. Here, we screened BE variants in HUDEP-2 cells for their ability to correct a spectrum of β-thalassemia mutations that were integrated into the genome as fragments of HBB. The identified targets were introduced into their endogenous genomic location using BEs and Cas9/homology-directed repair (HDR) to create cellular models with β-thalassemia/HbE. These β-thalassemia/HbE models were then used to assess the efficiency of correction in the native locus and functional β-globin restoration. Most bystander edits produced near target sites did not interfere with adult hemoglobin expression and are not predicted to be pathogenic. Further, the effectiveness of BE was validated for the correction of the pathogenic HbE variant in severe β0/βE-thalassaemia patient cells. Overall, our study establishes a novel platform to screen and select optimal BE tools for therapeutic genome editing by demonstrating the precise, efficient, and scarless correction of pathogenic point mutations spanning multiple regions of HBB including the promoter, intron, and exons.

Online assessments are needed during the prevailing pandemic situation to continue educational activities while ensuring safety. After conducting the online practical assessment (OPrA) in Biochemistry, we analyzed the students' responses. The blueprint of the OPrA was prepared by the faculty, referring to the various levels and domains of Bloom's taxonomy. Four components were chosen for the online assessment: digital spotters, enumerating the steps of objective structured practical examination, interpretation of quantitative estimation, and case discussion. Each faculty assessed about 12-13 students in separate breakout rooms over 15-20 min on all four components. Feedback on the conduct of the examination was collected from the students and faculty anonymously and analyzed. Out of the 200 students who attended the online assessment, only one scored less than 50%, majority of them scored between 71% and 90%. Under the individual exercises, the average score of students in "Spotters" was 9.8 out of 10; in "OSPE," 8.7 out of 10; in "Quantitative experiments," 15.2 out of 20 and in "Case discussion," 22.4 out of 30. Around 20% had previous experience attending the OPrA. They differed in their opinion from the rest of the students on five aspects; time allotted for the assessment (p value = 0.02, X[superscript 2] = 5.07), students using unfair means during the online viva (p value = 0.02, X[superscript 2] = 5.57), their computing skills (p value = 0.001, X[superscript 2] = 19.82), their performance (p value = 0.001, X[superscript 2] = 8.84), and overall conduct of the examination (p value = 0.001, X[superscript 2] = 15.55). OPrA tools may be designed referring to Bloom's taxonomy, and prior exposure to the online tools may benefit the students.

Naturally occurring point mutations in the HBG promoter switch hemoglobin synthesis from defective adult beta-globin to fetal gamma-globin in sickle cell patients with hereditary persistence of fetal hemoglobin (HPFH) and ameliorate the clinical severity. Inspired by this natural phenomenon, we tiled the highly homologous HBG proximal promoters using adenine and cytosine base editors that avoid the generation of large deletions and identified novel regulatory regions including a cluster at the -123 region. Base editing at -123 and -124 bp of HBG promoter induced fetal hemoglobin (HbF) to a higher level than disruption of well-known BCL11A binding site in erythroblasts derived from human CD34+ hematopoietic stem and progenitor cells (HSPC). We further demonstrated in vitro that the introduction of -123T > C and -124T > C HPFH-like mutations drives gamma-globin expression by creating a de novo binding site for KLF1. Overall, our findings shed light on so far unknown regulatory elements within the HBG promoter and identified additional targets for therapeutic upregulation of fetal hemoglobin.