Debriefer cognitive load during Traditional Reflective Debriefing vs. Rapid Cycle Deliberate Practice interdisciplinary team training.

BACKGROUND: Cognitive load impacts performance of debriefers and learners during simulations, but limited data exists examining debriefer cognitive load. The aim of this study is to compare the cognitive load of the debriefers during simulation-based team training (SbTT) with Rapid Cycle Deliberate Practice (RCDP) debriefing and Traditional Reflective Debriefing (TRD). We hypothesize that cognitive load will be reduced during RCDP compared to TRD. METHODS: This study was part of a large-scale, interdisciplinary team training program at Children's Healthcare of Atlanta Egleston Pediatric Emergency Department, with 164 learners (physicians, nurses, medical technicians, paramedics, and respiratory therapists (RTs)). Eight debriefers (main facilitators and discipline-specific coaches) led 28 workshops, which were quasi-randomized to either RCDP or TRD. Each session began with a baseline medical resuscitation scenario and cognitive load measurement using the NASA Task Load Index (TLX), and the NASA TLX was repeated immediately following either TRD or RCDP debriefing. Raw scores of the NASA TLX before and after intervention were compared. ANOVA tests were used to compare differences in NASA TLX scores before and after intervention between the RCDP and TRD groups. RESULTS: For all debriefers, mean NASA TLX scores for physical demands and frustration significantly decreased (- 0.8, p = 0.004 and - 1.3, p = 0.002) in TRD and mean perceived performance success significantly increased (+ 2.4, p < 0.001). For RCDP, perceived performance success increased post-debriefing (+ 3.6, p < 0.001), time demands decreased (- 1.0, p = 0.04), and frustration decreased (- 2.0, p < 0.001). Comparing TRD directly to RCDP, perceived performance success was greater in RCDP than TRD (3.6 vs. 2.4, p = 0.04). Main facilitators had lower effort and mental demand in RCDP and greater perceived success (p < 0.001). CONCLUSION: RCDP had greater perceived success than TRD for debriefers. Main facilitators also report reduced effort and baseline mental demand in RCDP. For less experienced debriefers, newer simulation programs, or large team training sessions such as our study, RCDP may be a less mentally demanding debriefing methodology for facilitators.

Development of an orally bioavailable mSWI/SNF ATPase degrader and acquired mechanisms of resistance in prostate cancer.

Mammalian switch/sucrose nonfermentable (mSWI/SNF) ATPase degraders have been shown to be effective in enhancer-driven cancers by functioning to impede oncogenic transcription factor chromatin accessibility. Here, we developed AU-24118, an orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of mSWI/SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients. Importantly, AU-24118 exhibited favorable pharmacokinetic profiles in preclinical analyses in mice and rats, and further toxicity testing in mice showed a favorable safety profile. As acquired resistance is common with targeted cancer therapeutics, experiments were designed to explore potential mechanisms of resistance that may arise with long-term mSWI/SNF ATPase PROTAC treatment. Prostate cancer cell lines exposed to long-term treatment with high doses of a mSWI/SNF ATPase degrader developed SMARCA4 bromodomain mutations and ABCB1 (ATP binding cassette subfamily B member 1) overexpression as acquired mechanisms of resistance. Intriguingly, while SMARCA4 mutations provided specific resistance to mSWI/SNF degraders, ABCB1 overexpression provided broader resistance to other potent PROTAC degraders targeting bromodomain-containing protein 4 and AR. The ABCB1 inhibitor, zosuquidar, reversed resistance to all three PROTAC degraders tested. Combined, these findings position mSWI/SNF degraders for clinical translation for patients with enhancer-driven cancers and define strategies to overcome resistance mechanisms that may arise.

Density functional theory study of the structure, stability, magnetic properties, and (hyper)polarizability of (sub-nm) rare-earth (RE) doped gold clusters: Au5RE with RE = Sc, Y, La-Lu.

Rare-earth doped materials are of immense interest for their potential applications in linear and nonlinear photonics. There is also intense interest in sub-nanometer gold clusters due to their enhanced stability and unique optical, magnetic, and catalytic properties. To leverage their emergent properties, here we report a systematic study of the geometries, stability, electronic, magnetic, and linear and nonlinear optical properties of Au5RE (RE = Sc, Y, La-Lu) clusters using density-functional theory. Several low-energy isomers consisting of planar or non-planar configurations are identified. For most doped clusters, the non-planar configuration is energetically favored. In the case of La-, Pm-, Gd-, and Ho-doped clusters, a competition between planar and non-planar isomers is predicted. A distinct preference for the planar configuration is predicted for Au5Eu, Au5Sm, Au5Tb, Au5Tm, and Au5Yb. The distinction between the planar and non-planar configurations is highlighted by the calculated highest frequencies, with the stretching mode of the non-planar configuration predicted to be stiffer than the planar configuration. The bonding analysis reveals the dominance of the RE-d orbitals in the formation of frontier molecular orbitals, which, in turn, facilitates retaining the magnetic characteristics governed by RE-f orbitals, preventing spin-quenching of rare earths in the doped clusters. In addition, the doped clusters exhibit small energy gaps between frontier orbitals, large dipole moments, and enhanced hyperpolarizability compared to the host cluster.

Development of an orally bioavailable mSWI/SNF ATPase degrader and acquired mechanisms of resistance in prostate cancer.

Mammalian switch/sucrose non-fermentable (mSWI/SNF) ATPase degraders have been shown to be effective in enhancer-driven cancers by functioning to impede oncogenic transcription factor chromatin accessibility. Here, we developed AU-24118, a first-in-class, orally bioavailable proteolysis targeting chimera (PROTAC) degrader of mSWI/SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients. Importantly, AU-24118 exhibited favorable pharmacokinetic profiles in preclinical analyses in mice and rats, and further toxicity testing in mice showed a favorable safety profile. As acquired resistance is common with targeted cancer therapeutics, experiments were designed to explore potential mechanisms of resistance that may arise with long-term mSWI/SNF ATPase PROTAC treatment. Prostate cancer cell lines exposed to long-term treatment with high doses of a mSWI/SNF ATPase degrader developed SMARCA4 bromodomain mutations and ABCB1 overexpression as acquired mechanisms of resistance. Intriguingly, while SMARCA4 mutations provided specific resistance to mSWI/SNF degraders, ABCB1 overexpression provided broader resistance to other potent PROTAC degraders targeting bromodomain-containing protein 4 (BRD4) and AR. The ABCB1 inhibitor, zosuquidar, reversed resistance to all three PROTAC degraders tested. Combined, these findings position mSWI/SNF degraders for clinical translation for patients with enhancer-driven cancers and define strategies to overcome resistance mechanisms that may arise.

A comparison of rapid cycle deliberate practice and traditional reflective debriefing on interprofessional team performance.

BACKGROUND: In simulation-based education, debriefing is necessary to promote knowledge acquisition and skill application. Rapid Cycle Deliberate Practice (RCDP) and Traditional Reflective Debriefing (TRD) are based in learning theories of deliberate practice and reflective learning, respectively. In this study, we compared the effectiveness of TRD versus RCDP on acquisition of conceptual knowledge and teamwork skills among interdisciplinary learners in the pediatric emergency department. METHODS: One hundred sixty-four learners including emergency department attending physicians, fellows, nurses, medical technicians, paramedics, and respiratory therapists, participated in 28 in-situ simulation workshops over 2 months. Groups were quasi-randomized to receive RCDP or TRD debriefing. Learners completed a multiple-choice test to assess teamwork knowledge. The TEAM Assessment Tool assessed team performance before and after debriefing. Primary outcomes were teamwork knowledge and team performance. RESULTS: Average pre-intervention baseline knowledge assessment scores were high in both groups (TRD mean 90.5 (SD 12.7), RCDP mean 88.7 (SD 15.5). Post-test scores showed small improvements in both groups (TRD mean 93.2 (SD 12.2), RCDP mean 89.9 (SD 13.8), as indicated by effect sizes (ES = 0.21 and 0.09, for TRD and RCDP, respectively). Assessment of team performance demonstrated a significant improvement in mean scores from pre-assessment to post-assessment for all TEAM Assessment skills in both TRD and RCDP arms, based on p-values (all p < 0.01) and effect sizes (all ES > 0.8). While pre-post improvements in TEAM scores were generally higher in the RCDP group based on effect sizes, analysis did not indicate either debriefing approach as meaningfully improved over the other. CONCLUSIONS: Our study did not demonstrate that either TRD versus RCDP was meaningfully better in teamwork knowledge acquisition or improving skill application and performance. As such, we propose Reflective Deliberate Practice as a framework for future study to allow learners to reflect on learning and practice in action.

Secretion of Sphinganine by Drug-Induced Cancer Cells and Modified Mimetic Sphinganine (MMS) as c-Src Kinase Inhibitor.

BACKGROUND: Cancer cells exhibit selective metabolic reprogramming to promote proliferation, invasiveness, and metastasis. Sphingolipids such as sphingosine and sphinganine have been reported to modulate cell death processes in cancer cells. However, the potential of extracellular sphinganine and its mimetic compounds as inducers of cancer cell death has not been thoroughly investigated. METHODS: We obtained extracellular conditioned medium from HCT-116 cells treated with the previously reported anticancer composition, goat urine DMSO fraction (GUDF). The extracellular metabolites were purified using a novel and in-house developed vertical tube gel electrophoresis (VTGE) technique and identified through LC-HRMS. Extracellular metabolites such as sphinganine, sphingosine, C16 sphinganine, and phytosphingosine were screened for their inhibitory role against intracellular kinases using molecular docking. Molecular dynamics (MD) simulations were performed to study the inhibitory potential of a novel designed modified mimetic sphinganine (MMS) (Pubchem CID: 162625115) upon c-Src kinase. Furthermore, inhibitory potential and ADME profile of MMS was compared with luteolin, a known c-Src kinase inhibitor. RESULTS: Data showed accumulation of sphinganine and other sphingolipids such as C16 sphinganine, phytosphingosine, and ceramide (d18:1/14:0) in the extracellular compartment of GUDF-treated HCT-116 cells. Molecular docking projected c-Src kinase as an inhibitory target of sphinganine. MD simulations projected MMS with strong (-7.1 kcal/mol) and specific (MET341, ASP404) binding to the inhibitory pocket of c-Src kinase. The projected MMS showed comparable inhibitory role and acceptable ADME profile over known inhibitors. CONCLUSION: In summary, our findings highlight the significance of extracellular sphinganine and other sphingolipids, including C16 sphinganine, phytosphingosine, and ceramide (d18:1/14:0), in the context of drug-induced cell death in HCT-116 cancer cells. Furthermore, we demonstrated the importance of extracellular sphinganine and its modified mimetic sphinganine (MMS) as a potential inhibitor of c-Src kinase. These findings suggest that MMS holds promise for future applications in targeted and combinatorial anticancer therapy.

Comparison of pupil size in patients of migraine with photophobia versus normal subjects and correlation of the pupil size to severity of headache.

PURPOSE: To compare the pupil size of patients having migraine with photophobia versus normal subjects and to correlate the pupil size to the severity of headache. METHODS: This was a prospective case-control study. One hundred eyes of 50 patients who had migraine with photophobia were compared with same number of control subjects who had no history of headache. Pupil size was measured using the IOL Master 700 in all cases. Severity of headache was evaluated by the Migraine Disability Assessment (MIDAS) test questionnaire, and MIDAS grades from 1 to 4 ranging from minimal disability to severe disability were obtained in all cases. The pupil sizes in all grades were compared. RESULTS: The mean pupil size was 4.89 ± 0.9 mm (95% confidence interval [CI]) in patients of migraine with photophobia compared to 3.8 ± 0.49 mm (95% CI) in normal subjects, with a P value of <0.0001, which was statistically significant. Among the 50 patients with migraine, according to MIDAS grades, 20 had Grade 4 or severe disability, 15 had Grade 3 or moderate disability, 10 had Grade 2 or mild disability, and five had Grade 1 or minimal disability. Pupil size in Grade 4 category was the largest with a mean value of 5.6 ± 0.79 mm (95% CI). CONCLUSION: The pupil size in patients of migraine with photophobia is larger than in normal subjects and could be a trigger for the migraine attacks. The larger the pupil size, the more severe is the migraine disability.

Meta-QTL analysis in wheat: progress, challenges and opportunities.

Wheat, an important cereal crop globally, faces major challenges due to increasing global population and changing climates. The production and productivity are challenged by several biotic and abiotic stresses. There is also a pressing demand to enhance grain yield and quality/nutrition to ensure global food and nutritional security. To address these multifaceted concerns, researchers have conducted numerous meta-QTL (MQTL) studies in wheat, resulting in the identification of candidate genes that govern these complex quantitative traits. MQTL analysis has successfully unraveled the complex genetic architecture of polygenic quantitative traits in wheat. Candidate genes associated with stress adaptation have been pinpointed for abiotic and biotic traits, facilitating targeted breeding efforts to enhance stress tolerance. Furthermore, high-confidence candidate genes (CGs) and flanking markers to MQTLs will help in marker-assisted breeding programs aimed at enhancing stress tolerance, yield, quality and nutrition. Functional analysis of these CGs can enhance our understanding of intricate trait-related genetics. The discovery of orthologous MQTLs shared between wheat and other crops sheds light on common evolutionary pathways governing these traits. Breeders can leverage the most promising MQTLs and CGs associated with multiple traits to develop superior next-generation wheat cultivars with improved trait performance. This review provides a comprehensive overview of MQTL analysis in wheat, highlighting progress, challenges, validation methods and future opportunities in wheat genetics and breeding, contributing to global food security and sustainable agriculture.

Structural tuning of ß-enamino diketones: exploration of solution and crystalline state photochromism.

A library of ß-enamino diketones was prepared via base-mediated, three-component reaction of 4-hydroxycoumarins with various aromatic/aliphatic amines and ß-nitrostyrenes under microwave irradiation conditions to investigate their photochemical properties. Among the prepared compounds, a thiophene derived ß-enamino diketone was found to be light-sensitive and to exhibit unique photochromic behavior, that is, positive photochromism in solution and negative photochromism in crystalline phase. In addition, this prepared photochromic compound was further covalently linked to a structure-related, piezochromic ß-enamino diketone moiety to explore its potential multi-stimuli responsive properties.

Effect of cryopreservation and capacitation on expression patterns of ATP synthesis associated genes in bubaline spermatozoa.

This study investigated the expression patterns of certain ATP synthesis associated genes (GAPDHS, PGK2, ENO4 and MDH2) in fresh and frozen-thawed bubaline spermatozoa vis-à-vis capacitation. Eight adult Murrah buffalo bulls, aged 5-7 years, were randomly selected from a bull farm and fresh semen was collected once a week for four weeks (n = 32) from the selected bulls. Simultaneously, frozen straws of the same bulls were collected (n = 32, four straws were pooled per sample). The samples were divided into four groups i.e., fresh non capacitated (control/group 1), fresh capacitated (group 2), frozen non capacitated (group 3) and frozen capacitated (group 4). In all groups mRNA extraction was done. The mRNA expression of GAPDHS was significantly higher in group 3 compared to the other groups, whereas the expression of ENO4 was significantly up-regulated in group 2 and 3 compared to the group 4. Similarly, the mRNA expression of PGK2 was significantly up-regulated in group 3 whereas in case of MDH2, it was significantly higher in group 2, 3 and 4 compared group 1. It can be concluded from our study that freezing and capacitation has a significant effect on the expression dynamics of the ATP synthesis-associated genes warranting necessary interventions in handling procedures to minimise the adverse effect of freezing on ATP synthesis process to ensure persistence of fertilizing ability of sperm.

Reduced Level of Prolylhydroxyproline in the Nail Clippings of Oral Cancer Patients and its Role as an Activator of Phospholipase C-ß2.

BACKGROUND: The oral cancer microenvironment plays an important role in the development and progression of the disease which depicts the heterogeneous nature of diseases. Several cellular and non-cellular factors, including dipeptides, have been reported to drive tumor progression and metastasis. Among various secreted molecules in the tumor microenvironment, prolylhydroxyproline (Pro-Hyp) is a collagen-degraded product with specific relevance to fibrosis and oral cancer. However, the detection of Pro-Hyp in the nails of oral cancer patients is a potential biomarker, and our understanding of the biological relevance of Pro-Hyp is highly limited. METHODS: Here, the authors have attempted to use a novel and in-house vertical tube gel electrophoresis (VTGE) protocol to evaluate the level of Pro-Hyp in the nails of oral cancer patients and healthy subjects. Furthermore, we employed molecular docking and molecular dynamics (MD) simulations to predict the biological function of Pro-Hyp. ADME profiles such as the druglikeness and leadlikeness of Pro-Hyp and a known PLC-ß2 activator, m-3M3FBS, were evaluated by the SWISS-ADME server. RESULTS: We report that among various key metabolites, Pro-Hyp, a dipeptide, is reduced in the nails of oral cancer patients. Molecular docking and MD simulations helped to suggest the potential role of Pro-Hyp as an activator of Phospholipase C-ß2 (PLC-ß2). Pro-Hyp displayed good binding affinity (-7.6 kcal/mol) with specific interactions by a conventional hydrogen bond with key residues, such as HIS311, HIS312, VAL641, and GLU743. MD simulations showed that the activator binding residues and stability of complexes are similar to the well-known activator m-3M3FBS of PLC-ß2. ADME profiles such as the druglikeness and leadlikeness of Pro-Hyp were found to be highly comparable and even better than those of m-3M3FBS. CONCLUSION: This study is one of the first reports on Pro-Hyp as a metabolite biomarker in the nails of oral cancer patients. Furthermore, the implications of Pro-Hyp are proposed to activate PLC-ß2 as a pro-tumor signaling cascade. In the future, diagnostic and therapeutic approaches may be explored as biomarkers and mimetic of Pro-Hyp.

Let us to the TWISST; Plan, Simulate, Study and Act.

Translational Work Integrating Simulation and Systems Testing (TWISST) is a novel application of simulation that augments how we discover, understand, and mitigate errors in our system. TWISST is a diagnostic and interventional tool that couples Simulation-based Clinical Systems Testing with simulation-based training (SbT). TWISST tests environments and work systems to identify latent safety threats (LSTs) and process inefficiencies. In SbT, improvements made to the work system are embedded in hard wire system improvements, ensuring optimal integration into clinical workflow. Methods: Simulation-based Clinical Systems Testing approach includes simulated scenarios, Summarize, Anchor, Facilitate, Explore, Elicit debriefing, and Failure Mode and Effect Analysis. In iterative Plan-Simulate-Study-Act cycles, frontline teams explored work system inefficiencies, identified LSTs, and tested potential solutions. As a result, system improvements were hardwired through SbT. Finally, we present a case study example of the TWISST application in the Pediatric Emergency Department. Results: TWISST identified 41 latent conditions. LSTs were related to resource/equipment/supplies (n = 18, 44%), patient safety (n = 14, 34%), and policies/procedures (n = 9, 22%). Work system improvements addressed 27 latent conditions. System changes that eliminated waste or modified the environment to support best practices mitigated 16 latent conditions. System improvements that addressed 44% of LSTs cost the department $11,000 per trauma bay. Conclusions: TWISST is an innovative and novel strategy that effectively diagnoses and remediates LSTs in a working system. This approach couples highly reliable work system improvements and training into 1 framework.

4-Chloro-3-nitrocoumarin as a precursor for synthesis of 2-arylchromeno[3,4-b]pyrrol-4(3H)-ones: a case of nitro group directed reductive coupling.

A series of 2-aryl substituted chromeno[3,4-b]pyrrol-4(3H)-ones were prepared in two steps by employing 4-chloro-3-nitrocoumarin as a precursor. The reaction involved the base-mediated reductive coupling of 4-chloro-3-nitrocoumarin with α-bromoacetophenone, followed by reductive intramolecular cyclization to afford the pyrrolocoumarin ring. When α-bromoacetophenone was replaced with α-cyanoacetophenone, (E)-4-(nitromethylene)-4H-chromen-2-amine was isolated as the major product. The molecular structures of the prepared compounds were characterized by X-ray crystallography and the mechanisms for their formation were proposed.

Can adoption of climate resilient management practices achieve carbon neutrality in traditional green revolution states of Punjab and Haryana?

Decreasing greenhouse gas (GHG) emissions and enhancing soil carbon (C) sequestration in cropland are necessary to achieve carbon neutrality at national scale. The major objective of this study is to quantify the GHG mitigation potential of adopted climate resilient (CR) practices in CR villages using Ex-ACT tool developed by Food and Agriculture Organization (FAO). Intensively cultivated area of Punjab and Haryana was selected for carrying out this study. In both the states, villages were selected by considering the climate for past 30 years. In the selected villages, a set of CR practices were implemented in annuals, perennials, irrigated rice, fertilizer use, land use change and livestock and quantified the GHG mitigation potential in these villages for next twenty years. The tool predicted that the CR practices adopted were successful in enhancing the overall sink (carbon balance) in all the study villages. The villages of Punjab had recorded higher mitigation potential as compared to the villages of Haryana. The overall sink potential in these villages ranged from -354 to -38309 Mg CO2-eq. The change in sink potential varied from 3.16 to 112% with lowest in Radauri and highest in Badhauchhi kalan village. The sink potential got doubled in Badhauchhi kalan village due to stopping rice straw burning and increase in area under perennials by 25%. The source potential varied from 6.33 to -7.44% across the study villages. Even with the implementation of NICRA, there was increase in source by 5.58 and 6.33% in Killi Nihal Singh Wala and Radauri due to irrigated rice, land use change and livestock. Majorly, rice straw burning was seen in most of the study villages, yet, with proper residue management and adoption of CR practices (mainly intermittent flooding) in rice cultivation resulted in emissions reduction up to 5-26% with enhanced productivity up to 15-18%, which can be considered for scaling up. Fertilizer management reduced the emissions by average of 13% across the study villages. Farm gate emission intensity per ton of milk and rice recorded highest emission intensity compared to annuals and perennials suggesting strict implementation of CR practices in rice cultivation and livestock sector. Implementation and scaling up of CR practices could potentially reduce the emissions and make the village C negative in intensive rice-wheat production system.

Introgression of Heterotic Genomic Segments from Brassica carinata into Brassica juncea for Enhancing Productivity.

Interspecific hybridization resulted in the creation of B. juncea introgression lines (ILs) generated from B. carinata with increased productivity and adaptability. Forty ILs were crossed with their respective B. juncea recipient parents to generate introgression line hybrids (ILHs) and the common tester (SEJ 8) was used to generate test hybrids (THs). Mid-parent heterosis in ILHs and standard heterosis in THs were calculated for eight yield and yield-related traits. Heterotic genomic regions were dissected using ten ILs with significant mid-parent heterosis in ILHs and standard heterosis in THs for seed yield. A high level of heterosis for seed yield was contributed by 1000 seed weight (13.48%) in D31_ILHs and by total siliquae/plant (14.01%) and siliqua length (10.56%) in PM30_ILHs. The heterotic ILs of DRMRIJ 31 and Pusa Mustard 30 were examined using polymorphic SNPs between the parents, and a total of 254 and 335 introgressed heterotic segments were identified, respectively. This investigation discovered potential genes, viz., PUB10, glutathione S transferase, TT4, SGT, FLA3, AP2/ERF, SANT4, MYB, and UDP-glucosyl transferase 73B3 that were previously reported to regulate yield-related traits. The heterozygosity of the FLA3 gene significantly improved siliqua length and seeds per siliqua in ILHs of Pusa Mustard 30. This research proved that interspecific hybridization is an effective means of increasing the diversity of cultivated species by introducing new genetic variants and improving the level of heterosis.

Spring Wheat's Ability to Utilize Nitrogen More Effectively Is Influenced by Root Phene Variation.

Genetic improvement for nitrogen use efficiency (NUE) can play a very crucial role in sustainable agriculture. Root traits have hardly been explored in major wheat breeding programs, more so in spring germplasm, largely because of the difficulty in their scoring. A total of 175 advanced/improved Indian spring wheat genotypes were screened for root traits and nitrogen uptake and nitrogen utilization at varying nitrogen levels in hydroponic conditions to dissect the complex NUE trait into its component traits and to study the extent of variability that exists for those traits in Indian germplasm. Analysis of genetic variance showed a considerable amount of genetic variability for nitrogen uptake efficiency (NUpE), nitrogen utilization efficiency (NUtE), and most of the root and shoot traits. Improved spring wheat breeding lines were found to have very large variability for maximum root length (MRL) and root dry weights (RDW) with strong genetic advance. In contrast to high nitrogen (HN), a low nitrogen (LN) environment was more effective in differentiating wheat genotypes for NUE and its component traits. Shoot dry weight (SDW), RDW, MRL, and NUpE were found to have a strong association with NUE. Further study revealed the role of root surface area (RSA) and total root length (TRL) in RDW formation as well as in nitrogen uptake and therefore can be targeted for selection to further the genetic gain for grain yield under high input or sustainable agriculture under limited inputs.

A Narrative Review of Osteonecrosis of the Jaw: What a Clinician Should Know.

Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon complication of antiresorptive therapy (ART) in patients receiving higher and more frequent doses of osteoclast inhibitors. The jaws are the most common site, as they have high bone turnover. The oral structures are exposed to various types of stresses, like mastication and dental diseases, which lead to microtrauma and increased bone remodeling. The hallmark feature of MRONJ is the area of exposed, necrotic, nonhealing, asymptomatic bone for more than eight weeks. Objective signs are pain in the jaw and oral cavity, loose teeth, gingival swelling, ulceration, soft tissue infection, and paresthesia in the trigeminal nerve branches' territory. Clinically, the MRONJ has been defined in four stages, from stage 0 to stage 3. Close coordination between the dentist and oncologist is critical for optimal treatment. Conservative management should be preferred over surgical management. There is significant underreporting and misdiagnosis of MRONJ cases in regular clinical practice. There needs to be more awareness among treating physicians about this sporadic complication of bisphosphonate therapy. This narrative review has given a detailed insight into the subject, starting with etiology, pathogenesis, incidence, clinical presentation, workup, staging, and various management strategies. The review article focuses mainly on practical aspects of MRONJ, which every clinician dealing with the disease must know. With a better awareness of this potential complication, healthcare practitioners dealing with at-risk patients can better diagnose, prevent, address, and provide necessary care.

Genome-wide association studies reveal putative QTLs for physiological traits under contrasting phosphorous conditions in wheat (Triticum aestivum L.).

A Genome-wide association (GWAS) study was conducted for phosphorous (P)-use responsive physiological traits in bread wheat at the seedling stage under contrasting P regimes. A panel of 158 diverse advanced breeding lines and released varieties, and a set of 10,800 filtered single nucleotide polymorphism (SNP) markers were used to study marker-trait associations over the eight shoot traits. Principle component analysis separated the two environments (P regimes) because of the differential response of the traits indicating the essentiality of the separate breeding programmes for each environment. Significant variations for genotypic, environmental, and genotype × environment (GEI) effects were observed for all the traits in the combined analysis of variance with moderately high broad sense heritability traits (0.50-0.73). With the different algorithms of association mapping viz., BLINK, FarmCPU, and MLM, 38 unique QTLs under non-limiting P (NLP) and 45 QTLs for limiting P (LP) conditions for various shoot traits were identified. Some of these QTLs were captured by all three algorithms. Interestingly, a Q.iari.dt.sdw.1 on chromosome 1D was found to explain the significant variations in three important physiological traits under non-limiting phosphorus (NLP) conditions. We identified the putative candidate genes for QTLs namely Q.iari.dt.chl.1, Q.iari.dt.sdw.16, Q.iari.dt.sdw.9 and Q.iari.dt.tpc.1 which are potentially involved in the mechanism regulating phosphorus use efficiency through improved P absorption due to improved root architectural traits and better mobilization such as sulfotransferase involved in postembryonic root development, WALLS ARE THIN1 (WAT1), a plant-specific protein that facilitates auxin export; lectin receptor-like kinase essentially involved in plant development, stress response during germination and lateral root development and F-box component of the SKP-Cullin-F box E3 ubiquitin ligase complex and strigolactone signal perception. Expression profiling of putative genes located in identified genomic regions against the wheat expression atlas revealed their significance based on the expression of these genes for stress response and growth development processes in wheat. Our results thus provide an important insight into understanding the genetic basis for improving PUE under phosphorus stress conditions and can shape the future breeding programme by developing and integrating molecular markers for these difficult-to-score important traits.

AIH in HIV: A Very Much Possible Entity.

Autoimmune Hepatitis (AIH) is a chronic liver disease Characterized by interface hepatitis, lymphoplasmacytic infiltrate, and hepatic rosettes. HIV infection is a state of immunosuppression; hence, the possibility of AIH is relatively rare, especially in patients with low CD4 counts. Therefore, we present an interesting case series of four patients with autoimmune liver disease with myriad presentations for the first time from India. We propose that despite the rarity of this presentation with immunosuppression, one should never miss such a treatable cause of liver disease leading to good clinical outcomes.