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Abiotic stress is the major bottleneck in obtaining the full potential of a standing crop. Various strategies have been investigated to impart abiotic stress tolerance. In the agricultural field, the stress conditions do not act in isolation rather they act synergistically in combinations against the wellbeing of the crop. The combined impact of abiotic stress conditions has been referred to as stress matrix or stress combination. Here, we have proposed a probable candidate that could be instrumental in imparting tolerance against stress matrix or stress combination. The investigation was made on a peroxisome localized glutathione reductase (GR) enzyme from the economically significant crop Oryza sativa. The protein was expressed in the E. coli system, purified and characterized. The enzyme was found to be active even at an elevated temperature of 55℃, demonstrating its abiotic stress tolerance properties. Further, the gene expression studies showed it to be upregulated under salinity, dehydration, low and high temperature. The expression was also investigated under various stress combinations and it was observed that the level of GR mRNA was found to be higher in the case of combined stress treatment as compared to individual stress conditions suggesting an additive effect phenomenon. The results obtained here put this peroxisomal GR in the spotlight for imparting abiotic stress combinations studies.

As the demand for food surges and the agricultural sector undergoes a transformative shift towards sustainability and efficiency, the need for precise and proactive measures to ensure the health and welfare of livestock becomes paramount. In the egg and hatchery industry, hyperspectral imaging (HSI) has emerged as a cutting-edge, non-destructive technique for fast and accurate egg quality analysis, including detecting chick embryo mortality. However, the high cost and operational complexity compared to conventional RGB imaging are significant bottlenecks in the widespread adoption of HSI technology. To overcome these hurdles and unlock the full potential of HSI, a promising solution is hyperspectral image reconstruction from standard RGB images. This study aims to reconstruct hyperspectral images from RGB images for non-destructive early prediction of chick embryo mortality. Initially, the performance of different image reconstruction algorithms, such as HRNET, MST++, Restormer, and EDSR were compared to reconstruct the hyperspectral images of the eggs in the early incubation period. Later, the reconstructed spectra were used to differentiate live from dead embryos eggs using the XGBoost and Random Forest classification methods. Among the reconstruction methods, HRNET showed impressive reconstruction performance with MRAE of 0.0955, RMSE of 0.0159, and PSNR of 36.79 dB. This study motivated the idea that harnessing imaging technology integrated with smart sensors and data analytics has the potential to improve automation, enhance biosecurity, and optimize resource management towards sustainable agriculture 4.0.

Abstract Background When feasible, guidelines recommend mitral valve repair (MVr) over mitral valve replacement (MVR) to treat primary mitral regurgitation (MR), based upon historic outcome studies and transthoracic echocardiography (TTE) reverse remodeling studies. Cardiovascular magnetic resonance (CMR) offers reference standard biventricular assessment with superior MR quantification compared to TTE. Using serial CMR in primary MR patients, we aimed to investigate cardiac reverse remodeling and residual MR post-MVr vs MVR with chordal preservation. Methods 83 patients with ≥ moderate-severe MR on TTE were prospectively recruited. 6-min walk tests (6MWT) and CMR imaging including cine imaging, aortic/pulmonary through-plane phase contrast imaging, T1 maps and late-gadolinium-enhanced (LGE) imaging were performed at baseline and 6 months after mitral surgery or watchful waiting (control group). Results 72 patients completed follow-up (Controls = 20, MVr = 30 and MVR = 22). Surgical groups demonstrated comparable baseline cardiac indices and co-morbidities. At 6-months, MVr and MVR groups demonstrated comparable improvements in 6MWT distances (+ 57 ± 54 m vs + 64 ± 76 m respectively, p = 1), reduced indexed left ventricular end-diastolic volumes (LVEDVi; − 29 ± 21 ml/m2 vs − 37 ± 22 ml/m2 respectively, p = 0.584) and left atrial volumes (− 23 ± 30 ml/m2 and − 39 ± 26 ml/m2 respectively, p = 0.545). At 6-months, compared with controls, right ventricular ejection fraction was poorer post-MVr (47 ± 6.1% vs 53 ± 8.0% respectively, p = 0.01) compared to post-MVR (50 ± 5.7% vs 53 ± 8.0% respectively, p = 0.698). MVR resulted in lower residual MR-regurgitant fraction (RF) than MVr (12 ± 8.0% vs 21 ± 11% respectively, p = 0.022). Baseline and follow-up indices of diffuse and focal myocardial fibrosis (Native T1 relaxation times, extra-cellular volume and quantified LGE respectively) were comparable between groups. Stepwise multiple linear regression of indexed variables in the surgical groups demonstrated baseline indexed mitral regurgitant volume as the sole multivariate predictor of left ventricular (LV) end-diastolic reverse remodelling, baseline LVEDVi as the most significant independent multivariate predictor of follow-up LVEDVi, baseline indexed LV end-systolic volume as the sole multivariate predictor of follow-up LV ejection fraction and undergoing MVR (vs MVr) as the most significant (p

The emergence of federated learning (FL) technique in fog-enabled healthcare system has leveraged enhanced privacy towards safeguarding sensitive patient information over heterogeneous computing platforms. In this paper, we introduce the FedHealthFog framework, which was meticulously developed to overcome the difficulties of distributed learning in resource-constrained IoT-enabled healthcare systems, particularly those sensitive to delays and energy efficiency. Conventional federated learning approaches face challenges stemming from substantial compute requirements and significant communication costs. This is primarily due to their reliance on a singular server for the aggregation of global data, which results in inefficient training models. We present a transformational approach to address these problems by elevating strategically placed fog nodes to the position of local aggregators within the federated learning architecture. A sophisticated greedy heuristic technique is used to optimize the choice of a fog node as the global aggregator in each communication cycle between edge devices and the cloud. The FedHealthFog system notably accounts for drop in communication latency of 87.01%, 26.90%, and 71.74%, and energy consumption of 57.98%, 34.36%, and 35.37% respectively, for three benchmark algorithms analyzed in this study. The effectiveness of FedHealthFog is strongly supported by outcomes of our experiments compared to cutting-edge alternatives while simultaneously reducing number of global aggregation cycles. These findings highlight FedHealthFog's potential to transform federated learning in resource-constrained IoT environments for delay-sensitive applications.

Introduction: The outcomes in advanced NSCLC have improved owing to the availability of more effective systemic and improved supportive care. This has increased the number of patients who seek treatment in the third line and beyond setting. We conducted this study to compare the quality of life (QoL), toxicity, and outcomes in patients receiving chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) in this setting. Methods: In this phase 3, randomized, open-label study, patients with stage III or IV NSCLC with disease progression on at least two prior lines of chemotherapy, with a life expectancy of at least 3 months, without prior EGFR TKI exposure, and stable brain metastases (if any) were included. Patients were randomized to receive chemotherapy (gemcitabine or docetaxel or paclitaxel or vinorelbine) or an EGFR TKI (erlotinib or gefitinib). The primary end point was the change in QoL at 8 to 10 weeks; the secondary outcomes were safety and overall survival (OS). Patients underwent clinical evaluation at every visit, and toxicity was assessed as per Common Terminology Criteria for Adverse Events version 4.03. A radiological tumor response assessment was done every 8 to 12 weeks from the start of therapy. The QoL was assessed using the EORTC QLQ C30 and LC13 questionnaires. The change in QoL scores was calculated as the difference between scores at baseline and scores at 8 to 10 weeks (Δ) for each QoL domain. The Mann-Whitney U test was used to compare the mean difference (Δ) for each domain. OS and progression-free survival (PFS) were determined using the Kaplan-Meier method and Cox proportional regression analysis. Results: A total of 246 patients were enrolled in the study, with 123 in each arm. There was a male predominance with 69.1% male patients in the chemotherapy arm and 70.7% in the EGFR TKI arm. The median age of patients in the chemotherapy arm was 54 years and 55 years in the chemotherapy and EGFR TKI arms, respectively. There was no significant difference in the change in QoL at baseline and the second visit (Δ) in both arms in all domains of EORTC QLQ C30 except cognitive function (p = 0.0045) and LC13 except alopecia (0.01249). The mean Δ Global Health Status was −28 in the chemotherapy arm and −26.8 in the EGFR TKI arm; this was not statistically significant (p = 0.973). The median follow-up was 88.1 months (95% confidence interval [CI]: 39.04–137.15). On the intention-to-treat analysis, the median PFS was 3.13 months (95% CI: 2.15–4.11) in the chemotherapy arm and 2.26 months (95% CI: 2.1–2.43) in the EGFR TKI arm, with hazard ratio at 1.074 (95% CI: 0.83–1.38) (p = 0.58). There were 120 deaths in each arm. The median OS was 7.63 months (95% CI: 5.96–9.30) in the chemotherapy arm and 7.5 months in the EGFR TKI arm (95% CI: 5.85–9.14); hazard ratio at 1.033 (95% CI: 0.80–1.33) (p = 0.805). The toxicity profile was similar in both arms except for a significantly higher incidence of fatigue (p = 0.043), peripheral neuropathy (0.000), alopecia, hypokalemia (0.037), and pedal edema (0.007) in the chemotherapy arm and dry skin (p = 0.000) and skin rash (p = 0.019) in the EGFR TKI arm. Conclusions: There was no significant difference in most QoL scales (except cognitive function and alopecia), OS, and PFS of patients with advanced NSCLC receiving an EGFR TKI as compared with chemotherapy TKI in the third-line setting. The toxicity profile is consistent with the known toxicities of the agents.

Crigler-Najjar syndrome is a rare disorder of bilirubin metabolism caused by uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) mutations characterized by hyperbilirubinemia and jaundice. No cure currently exists; treatment options are limited to phototherapy, whose effectiveness diminishes over time, and liver transplantation. Here, we evaluated the therapeutic potential of systemically administered, lipid nanoparticle-encapsulated human UGT1A1 (hUGT1A1) mRNA therapy in a Crigler-Najjar mouse model. Ugt1 knockout mice were rescued from lethal post-natal hyperbilirubinemia by phototherapy. These adult Ugt1 knockout mice were then administered a single lipid nanoparticle-encapsulated hUGT1A1 mRNA dose. Within 24 h, serum total bilirubin levels decreased from 15 mg/dL (256 μmol/L) to

The ocular surface microbiome, unlike that of the skin or gut, has not been well characterized. Culture experiments historically suggested a nearly sterile ocular surface, but initial application of molecular methods such as 16S ribosomal RNA and high-throughput sequencing demonstrated a surprisingly rich ocular surface microbiome. However, a major limitation in studying such a low-biomass niche is the potential for artifactual results when amplification-based techniques such as ribosomal polymerase chain reaction and shotgun sequencing are used. It will be essential to establish standards across the field for sample collection, positive and negative controls, and limitation of contamination in both the laboratory setting and computational analysis. New developments in ocular microbiome research, including the generation of reference reagents and fluoroscopic imaging techniques, provide improved means to validate sequencing results and to visualize complex interactions between host cells and bacteria. Through more thorough characterization of the ocular surface microbiome, the connections between a dysregulated surface and ophthalmic disease may be better understood. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Summary: This study investigated and compared the wound healing kinetics of pigmented (PG) and non-pigmented (NP) skin in guinea pigs, focusing on histological and transcriptional changes. Full-thickness wounds created on PG and NP skin were evaluated at various time points post-injury. Fontana-Masson staining and ultrastructural analysis suggested the presence of melanin and melanosomes in PG skin, which coincided with an upregulation of melanogenic genes cKIT, TYR, and DCT. On day 9 post-wound, PG skin exhibited a rapid transition from the inflammatory to proliferative phase, which correlated with the reappearance of epidermal pigmentation whereas the NP skin exhibited a delayed neo-epidermis formation. Furthermore, the study revealed that melanocyte-derived growth factors (conditioned media) positively regulated keratinocyte migration while inhibiting fibroblast differentiation. These effects were more prominent in tyrosine-treated (hyperpigmented) melanocyte-CM as was TGF- β expression. These findings provide valuable insights into the mechanisms underlying skin repair and pigmentation.

Introduction: Gothic arch Tracing has been a common modality in the recording of centric jaw relation. There has been two ways of recording the gothic tracing. They are extra oral and intra oral tracing. Among the extra oral tracers hight tracers are the most used tracers. Aim: Intra-oral and extra-oral tracers have a number of individual advantages and limitations. With the idea to overcome the short comings of both the tracers, hybrid tracers were made. Hybrid tracers could be a good alternative to the Hight-tracer in recording centric relation and can provide better clinical and teaching experience to the students. Methodology: The hybrid tracer is a two-component assembly, upper and lower component. The upper component has a central bearing plate and stylus in continuation with the central bearing plate. The lower component has central bearing device with three central bearing points one anteriorly and two posteriorly, and it has a tracing platform (15 × 35 mm) in continuation with the central bearing device. The length of these upper and lower components ismade to confine within the incisal rod of semi adjustable articulator. Result: hybrid tracers showed more accuracy while recording the centric jaw relation. There was more stability and equalization of pressure during the movement due to a tripod effect of three screws. Hence it provided more precise recording and being less technique sensitive. It was also more comfortable and acceptable by the patient. Conclusion: hybrid tracers hence will provide more accuracy and precision in recording of horizontal jaw relation. This will in turn help in fabricating a successful prosthesis and enhance the well-being of the patient. This tracer will also be significant in institutions for educational purpose. Clinical implication: Hybrid tracers are simple, non-technique sensitive, provide balance, equalization of pressure, stabilize the occlusal rims well, are close to the centre of rotation providing precise record and provide easy access and visibility to the operator which will help the operator in guiding the patient well for a correct jaw relation.

Summary: Mutations of the transcription factor FoxP3 in patients with “IPEX” (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome) disrupt regulatory T cells (Treg), causing an array of multiorgan autoimmunity. To understand the functional impact of mutations across FoxP3 domains, without genetic and environmental confounders, six human FOXP3 missense mutations are engineered into mice. Two classes of mutations emerge from combined immunologic and genomic analyses. A mutation in the DNA-binding domain shows the same lymphoproliferation and multiorgan infiltration as complete FoxP3 knockouts but delayed by months. Tregs expressing this mutant FoxP3 are destabilized by normal Tregs in heterozygous females compared with hemizygous males. Mutations in other domains affect chromatin opening differently, involving different cofactors and provoking more specific autoimmune pathology (dermatitis, colitis, diabetes), unmasked by immunological challenges or incrossing NOD autoimmune-susceptibility alleles. This work establishes that IPEX disease heterogeneity results from the actual mutations, combined with genetic and environmental perturbations, explaining then the intra-familial variation in IPEX.

Abstract Background The underlying pathophysiology of post-coronavirus disease 2019 (long-COVID-19) syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus CMR spectroscopy (31P-CMRS) allows non-invasive assessment of the myocardial energetic state. The main aim of the study was to assess whether long COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and energy metabolism. Methods Prospective case–control study. A total of 20 patients with a clinical diagnosis of long COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and 10 matching healthy controls underwent 31P-CMRS and CMR at 3T at a single time point. All patients had been symptomatic with acute COVID-19, but none required hospital admission. Results Between the long COVID-19 syndrome patients and matched contemporary healthy controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T1 mapping and late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with long COVID-19 syndrome showed subepicardial hyperenhancement on late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, extracellular volume fraction, native T1, T2 or cardiac energetics. Conclusions In this prospective case–control study, the overwhelming majority of patients with a clinical long COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics.

Summary: Background: Identification of convulsive epilepsy in sub-Saharan Africa relies on access to resources that are often unavailable. Infrastructure and resource requirements can further complicate case verification. Using machine-learning techniques, we have developed and tested a region-specific questionnaire panel and predictive model to identify people who have had a convulsive seizure. These findings have been implemented into a free app for health-care workers in Kenya, Uganda, Ghana, Tanzania, and South Africa. Methods: In this retrospective case-control study, we used data from the Studies of the Epidemiology of Epilepsy in Demographic Sites in Kenya, Uganda, Ghana, Tanzania, and South Africa. We randomly split these individuals using a 7:3 ratio into a training dataset and a validation dataset. We used information gain and correlation-based feature selection to identify eight binary features to predict convulsive seizures. We then assessed several machine-learning algorithms to create a multivariate prediction model. We validated the best-performing model with the internal dataset and a prospectively collected external-validation dataset. We additionally evaluated a leave-one-site-out model (LOSO), in which the model was trained on data from all sites except one that, in turn, formed the validation dataset. We used these features to develop a questionnaire-based predictive panel that we implemented into a multilingual app (the Epilepsy Diagnostic Companion) for health-care workers in each geographical region. Findings: We analysed epilepsy-specific data from 4097 people, of whom 1985 (48·5%) had convulsive epilepsy, and 2112 were controls. From 170 clinical variables, we initially identified 20 candidate predictor features. Eight features were removed, six because of negligible information gain and two following review by a panel of qualified neurologists. Correlation-based feature selection identified eight variables that demonstrated predictive value; all were associated with an increased risk of an epileptic convulsion except one. The logistic regression, support vector, and naive Bayes models performed similarly, outperforming the decision-tree model. We chose the logistic regression model for its interpretability and implementability. The area under the receiver operator curve (AUC) was 0·92 (95% CI 0·91–0·94, sensitivity 85·0%, specificity 93·7%) in the internal-validation dataset and 0·95 (0·92–0·98, sensitivity 97·5%, specificity 82·4%) in the external-validation dataset. Similar results were observed for the LOSO model (AUC 0·94, 0·93–0·96, sensitivity 88·2%, specificity 95·3%). Interpretation: On the basis of these findings, we developed the Epilepsy Diagnostic Companion as a predictive model and app offering a validated culture-specific and region-specific solution to confirm the diagnosis of a convulsive epileptic seizure in people with suspected epilepsy. The questionnaire panel is simple and accessible for health-care workers without specialist knowledge to administer. This tool can be iteratively updated and could lead to earlier, more accurate diagnosis of seizures and improve care for people with epilepsy. Funding: The Wellcome Trust, the UK National Institute of Health Research, and the Oxford NIHR Biomedical Research Centre.

Advancement in the fields of electronic communication, data processing, and internet technologies enable easy access to and interaction with a variety of physical devices throughout the globe. Our whole world is enveloped by a blanket of innumerable smart devices equipped with the sensors and actuators. Extensive research on the Internet of things (IoT) with cloud technologies, make it possible to accumulate tremendous data created from this heterogeneous environment and transform it into precious knowledge by utilizing data mining technologies. Furthermore, this generated knowledge will play a key role in intelligent decision making, system performance boosting, and optimum management of resources and services. With this background, this paper presents a systematic and detailed review of various data mining techniques employed in the large and small scale IoT applications to formulate an intelligent environment. It also presents an overview of cloud-assisted IoT Big data mining system to better understand the importance of data mining for an IoT environment.

We report a design for an orchestrator controlled robotic network that organises and manages a set of activities through a task allocation model for the robotic nodes. The model also helps to study the robotic-orchestration with the help of centralised and decentralised approaches. Additionally, our model incorporates an innovative collision avoidance algorithm that avoids collision between parallel running robots without any communication between them. The results of the orchestrated, centralised and decentralised approaches are compared using the Paired signed and Wilcoxon signed rank tests. Simulated results, when compared with the experimental data, show that the orchestrated approach is better than the decentralised approach in terms of communication bandwidth and performance’s consistency. In addition, the orchestrated approach is better than the centralised approach, in terms of both communication overloads and task execution time.

Background: Improved emergency care of children with acute illness or injuries is needed for countries in Africa to continue to reduce childhood mortality rates. Quality improvement efforts will depend on robust baseline data, but little has been published on the breadth and severity of paediatric illness seen in Mozambique. Methods: This was a retrospective review of routinely collected provider shift summary data from the Paediatric Emergency Department (PED) at Hospital Central de Maputo (HCM), the principal academic and referral hospital in the country. All children 0–14 years of age seen in the 12-month period from August 2018–July 2019 were included. Descriptive statistical analyses were performed. Results: Data from 346 days and 64,966 patient encounters were analyzed. The large majority of patients (96.4%) presented directly to the PED without referral from a lower level facility. An average of 188 patients was seen per day, with significant seasonal variation peaking in March (292 patients/day). The most common diagnoses were upper respiratory infections (URI), gastroenteritis, asthma, and dermatologic problems. The highest acuity diagnoses were neurologic problems (59%), asthma (57%), and neonatal diagnoses (50%). Diagnoses with the largest proportion of admissions included neurologic problems, malaria, and neonatal diagnoses. Rapid malaria antigen tests were the most commonly ordered laboratory test across all diagnostic categories; full blood count (FBC) and chemistries were also commonly ordered. Urinalysis and HIV testing were rarely done in the PED. Conclusion: This epidemiologic profile of illness seen in the HCM PED will allow for improved resource utilisation. We identified opportunities for evidence-based care algorithms for common diagnoses such as respiratory illness to improve patient care and flow. The PED may also be able to optimize laboratory and radiology evaluation for patients and develop standardized admission criteria by diagnosis.

Spontaneous spinal epidural hematoma is a rare predominantly idiopathic entity which can prompt acute neurologic symptoms and if not managed in time can lead to devastating outcomes. High index of suspicion is required for early diagnosis on MRI for a prompt management of patients showing sudden neurologic deficits. Our patient was 42-year-old female who presented with sudden onset of numbness followed by weakness in both lower limbs and urinary retention without any comorbidity or any medication. MRI whole spine done within 14 hours of symptom onset showed ventral epidural hematoma without any vascular malformation. Immediate decompressive laminectomy with evacuation of hematoma improved power in both lower limbs with regaining bowel and bladder function. The key here is timely surgical decompression of the hematoma for a favorable neurosurgical outcome. Although there is a recent development towards non–surgical treatment, it needs to be well established yet and require such approach on case-to-case basis.

Restrictive cardiomyopathy (RCM) is an uncommon form of cardiomyopathy and is characterized by impaired ventricular filling due to increased myocardial stiffness. In India, RCM is frequently observed in the young and endemic endomyocardial fibrosis is seen in a significant number of cases. We report a case of 15-year-old boy who presented with such a treatable cause of heart failure. On 2D Echocardiography we observed signs of restrictive cardiomyopathy (RCM) and severe mitral and tricuspid regurgitation. RCM is an uncommon form of cardiomyopathy and is usually associated with a poor prognosis. Genetic workup revealed myeloid neoplasm with eosinophilia. Eosinophilic cardiomyopathy is an infrequently reported entity.

Kraft lignin (KL), is the major pollutant in pulp and paper effluent and due to its heterogeneous structure, it is resistant to the depolymerization process. It has drawn much attention from the researcher due to its challenging degradation process. In this study, a KL-degrading bacterium was isolated and screened from paper mill sludge. This bacterium was identified as ligninolytic Bacillus aryabhattai using biochemical and 16SrRNA gene analysis. B. aryabhattai showed maximum activities of lignin peroxidase-LiP (0.74 IU mL−1) and manganese peroxidase-MnP (9.2 IU mL−1) on the 4th day, and 5th day, respectively. A total 84% of KL (500 mg L−1) reduction was observed after 14 days. The KL bio-degradation was confirmed based on changes in chemical stracture of KL and new metabolites identification using FTIR and GC–MS, respectively. The study concluded that B. aryabhattai maybe becomes a potential biological agent in KL biodegradation and treatment of other lignin-containing industrial effluents.

Summary: Background: Investing in late-stage clinical trials, trial sites, and production capacity for new health products could improve access to vaccines, therapeutics, and infectious disease diagnostics in middle-income countries. This study assesses the case for such investment in three of these countries: India, Kenya, and South Africa. Methods: We applied investment case modelling and assessed how many cases, deaths, and disability-adjusted life years (DALYs) could be averted from the development and manufacturing of new technologies (therapeutics and vaccines) in these countries from 2021 to 2036, for five diseases—HIV, tuberculosis, malaria, pneumonia, and diarrhoeal diseases. We also estimated the economic benefits that might accrue from making these investments and we developed benefit–cost ratios for each of the three middle-income countries. Our modelling applies two investment case perspectives: a societal perspective with all costs and benefits measured at the societal level, and a country perspective to estimate how much health and economic benefit accrues to each middle-income country for every dollar invested in clinical trials and manufacturing by the middle-income country government. For each perspective, we modelled two scenarios: one that considers only domestic health and economic benefits; and one that includes regional health and economic benefits. In the regional scenarios, we assumed that new products developed and manufactured in India would benefit eight countries in south Asia, whereas new products developed and manufactured in Kenya would benefit all 21 countries in the Common Market for Eastern and Southern Africa (COMESA). We also assumed that all 16 countries in the Southern African Development Community (SADC) would benefit from products developed and manufactured in South Africa. Findings: From 2021 to 2036, product development and manufacturing in Kenya could avert 4·44 million deaths and 206·27 million DALYs in the COMESA region. In South Africa, it could prevent 5·19 million deaths and 253·83 million DALYs in the SADC region. In India, it could avert 9·76 million deaths and 374·42 million DALYs in south Asia. Economic returns would be especially high if new tools were produced for regional markets rather than for domestic markets only. Under a societal perspective, regional returns outweigh investments by a factor of 20·51 in Kenya, 33·27 in South Africa, and 66·56 in India. Under a country perspective, the regional benefit–cost ratios amount to 60·71 in India, 8·78 in Kenya, and 11·88 in South Africa. Interpretation: Our study supports the creation of regional hubs for clinical trials and product manufacturing compared with narrow national efforts. Funding: Bill & Melinda Gates Foundation.

Aim & objectives: Clinical trials had concluded a significant relationship between implant failure and bruxism. A three-dimensional (3D) finite element analysis (FEA) was done to evaluate the stress distribution in straight and angled abutments around titanium and carbon fiber-reinforced polyetheretherketone (CFR-PEEK) implant with 2 different prosthetic crowns under parafunctional loading. Materials and method: Twelve 3D models of bone block were created representing the maxillary right premolar area with osseointegrated implants. The models were divided in two group; CFR-PEEK implant (n ​= ​6) and group titanium implant (n ​= ​6).Each group was subdivided based on implants with three different abutments (straight, 15°, 25° angled abutments) and having two different prosthetic crowns: porcelain fused to metal (PFM) and polyetheretherketone (PEEK). A vertical load of 1000 ​N was applied to the central fossa and an oblique load of 500 ​N (30°) was applied to the buccal incline of the palatal cusp. The von Mises stresses and principal stresses were analyzed using ANSYS software. Results: CFR-PEEK and titanium implants produced similar stress in bone under vertical and oblique loading. Straight abutment showed better results than 15° and 25° angled abutments in all the groups. PEEK crown produced lesser stress than PFM crown under vertical and oblique loading. Conclusion: The study concluded that straight abutment along with PEEK crown could be given in patients with bruxism to reduce the stress concentration in bone, thus preventing possible implant failure. Titanium and CFR-PEEK implants with straight abutments if given, then it should be provided with an occlusal splint.

Background: Limited literature exists on Cerebrospinal fluid (CSF) findings in COVID-19 patients with neurological symptoms. In this review, we conducted a descriptive analysis of CSF findings in patients with COVID-19 to understand prognosis and explore therapeutic options. Methods: We searched PubMed, Google Scholar, and Scopus databases using the keywords “SARS-CoV-2 in cerebrospinal fluid” and “SARS-CoV-2 and CNS Complications”'' for reports of CSF findings in COVID-19 related neurological manifestations. Descriptive analyses were conducted to observe the CSF protein and cell counts based on age, gender, severity, fatality of COVID-19, and whether central (CNS) or peripheral nervous system (PNS) was associated. Results: A total of 113 patients were identified from 67 studies. Of these, 7 patients (6.2%) were fatal COVID-19 cases and 35 patients (31%) were considered severe COVID-19 cases. CSF protein was elevated in 100% (7/7) of the fatal cases with an average of 61.28 mg/dl and in 65.0% (52/80) in non-fatal cases with an average 56.73 mg/dl. CSF protein levels were elevated in 74.5% (38/51) patients with non-severe COVID-19 and 68.6% (24/35) in those with a severe COVID-19 infection. CSF cell count was increased in 43% of fatal cases, 25.7% severe cases, and 29.4% of non-severe cases. Conclusion: Our analysis showed that the most common CSF findings situation in COVID-19 infection is elevated protein with, very occasionally, mild lymphocyte predominant pleocytosis. Further studies to elucidate the pathophysiology of neurological complications in COVID-19 are recommended.

Purpose: Palbociclib is a selective cyclin-dependent kinase 4/6 inhibitor approved for metastatic ER+/HER2- breast cancer. Preclinical evidence suggests a possible synergistic effect of palbociclib when combined with radiation therapy (RT); however, the toxicity of this pairing is unknown. We report preliminary results on the use of this combination. Methods and Materials: Records of patients treated with palbociclib at our institution from 2015 to 2018 were retrospectively reviewed. Patients who received RT for symptomatic metastases concurrently or within 14 days of palbociclib were included. Local treatment effect was assessed by clinical examination and subsequent computed tomography/magnetic resonance imaging. Toxicity was graded based on Common Terminology Criteria for Adverse Events version 5.0. Results: A total of 16 women received palliative RT in close temporal proximity to palbociclib administration. Four patients received palbociclib before RT (25.0%), 5 concurrently (31.3%), and 7 after RT (43.8%). The median interval from closest palbociclib use to RT was 5 days (range, 0-14). The following sites were irradiated in decreasing order of frequency: bone (11 axial skeleton [9 vertebra and 2 other]; 4 pelvis; 3 extremity), brain (4: 3 whole brain RT and 1 stereotactic radiosurgery), and mediastinum (1). The median and mean follow-up time is 14.7 and 17.6 months (range, 1.7-38.2). Pain relief was achieved in all patients. No radiographic local failure was noted in the 13 patients with evaluable follow-up imaging. Leukopenia, neutropenia, and thrombocytopenia were seen in 4 (25.0%), 5 (31.3%), and 1 (6.3%) patient before RT. After RT, 5 (31.3%), 1 (6.3%), and 3 (18.8%) patients were leukopenic, neutropenic, and thrombocytopenic, respectively. All but 2 (grade 2) hematologic toxicities were grade 1. No acute or late grade 2+ cutaneous, neurologic, or gastrointestinal toxicities were noted. Toxicity results did not differ based on disease site, palbociclib-RT temporal association, or irradiated site. Conclusions: The use of RT in patients receiving palbociclib resulted in minimal grade 2 and no grade 3+ toxicities. This preliminary work suggests that symptomatic patients receiving palbociclib may be safely irradiated.

Aim and objectives: The study evaluated the stress distribution in an endodontically treated tooth with four different post systems and restored with two different prosthetic crown materials using finite element analysis (FEA). Material and methods: A total of eight 3D FEA models of maxillary central incisor were created and divided into two groups; group porcelain fused to metal (PFM) crown (n = 4) and group PEEK crown (n = 4). The endodontically treated tooth was restored using four different post materials such as fiber-reinforced composite (FRC), carbon fiber-reinforced polyetheretherketone (CFR-PEEK), glass fiber reinforced polyetheretherketone (GFR-PEEK) and polyetherketoneketone (PEKK) and composite resin core. A static load of 100 N was applied and von Mises stress was calculated. The stress ratio in dentin was analyzed by using the Mohr-Coulomb failure theory. Results: In dentin, under the applied forces for both, PFM group and PEEK group, it was observed that CFR-PEEK post exhibited minimum von Mises stress while PEKK post exhibited maximum von Mises stress values. The result obtained showed that low stresses were detected using CFR-PEEK post than FRC, GFR-PEEK, and PEKK posts. Conclusion: Stress observed in dentin, when CFR-PEEK post was used was lesser in comparison to the FRC post. It was noted that PEEK crown and the PFM crown showed similar effect in dentin in stress generation. Hence, PEEK crown can be used as an alternative to the PFM crown.

Background: Mycobacterium tuberculosis (Mtb) drug resistance is a global concern. Moreover, multiple drug resistant (MDR), extensively drug resistant (XDR), and totally drug resistant (TDR) Mtb cases are on the rise in developing countries like India. Most of these cases are identified only 3–6 months after initiation of treatment owing to incomplete/failed clinical response and incomplete information from phenotypic drug resistance assays and/or targeted Mtb mutation analysis. Here, we report the development of an in-house whole genome sequencing (WGS) assay and bioinformatics pipeline that helped resolve the phenotype-genotype discrepancy in a clinical isolate. Methodology and results: A sample from a suspected drug resistant Mtb case tested by line probe assay (LPA) showed the absence of both the mutant and wild type alleles for an rpoB gene mutation site. An in-house next generation sequencing (NGS) assay was used for WGS of this isolate. Bioinformatics analysis revealed that the isolate harboured a novel insertional mutation in the 81-bp hotspot region of the rpoB gene and a S315T mutation in the katG gene, which could explain resistance to rifampicin and isoniazid, respectively. These results correlated with the clinical diagnosis, LPA, solid culture drug susceptibility testing, and pyrosequencing carried out on the sample. The WGS data also provided information regarding the isolate’s lineage and indicated an absence of known mutations conferring resistance to other antitubercular drugs. Conclusion: WGS is a highly sensitive, specific, and unbiased approach for identification of all possible drug resistance-conferring mutations, which can help clinicians make more informed treatment-related decisions.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has affected the care of patients with noncommunicable diseases, including those suffering from kidney-related ailments. Many parts of the world, including India, adopted lockdown to curb community transmission of disease. The lockdown affected transportation, access to health care facilities, and availability of medicines and consumables as well as outpatient and inpatient services. We aimed to analyze the effect of lockdown imposed due to the COVID-19 pandemic on the care of patients with kidney diseases in India. Methods: We surveyed 19 major hospitals (8 in the public and 11 in the private sector) to determine the effect of lockdown on the care of patients with kidney disease, including those on dialysis after the first 3 weeks of lockdown. Results: The total number of dialysis patients in these centers came down from 2517 to 2404. Approximately 710 (28.2%) patients missed 1 or more dialysis sessions, 69 (2.74%) required emergency dialysis sessions, 104 (4.13%) stopped reporting for dialysis, and 9 (0.36%) were confirmed to have died. Outpatient attendance in the surveyed hospital came down by 92.3%, and inpatient service reduced by 61%. Tele-consultation was started but was accessed by only a small number of patients. Conclusion: Lack of preparedness before lockdown resulted in an interruption in health care services and posed an immediate adverse effect on the outcome of dialysis patients and patients with kidney disease in India. The long-term impact on the health of patients with less severe forms of kidney disease remains unknown.

Background: Hydrophilic implant surface has gained increasing interest as a factor to stimulate osseointegration. Purpose: The study was done to formulate hydrophilic gel to be applied on to the dental implant surface, to enhance bone to implant contact (BIC). Materials and methods: In first part of study, Acemannan and Moringa oleifera hydro gel formulated in different proportions were coated on the titanium disk and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay was done to evaluate cell viability.Cytotoxicity of aqueous extracts of two plants were tested against UMR106 cells. In second part of study, the prototype titanium implants were placed in tibia and femur of 8 male rabbits. Hydrophilic gel formulated from Acemannan and Moringa oleifera were coated on the study groups of implants. Histomorphometric analysis was carried out of the enbloc sections specimens. Student's unpaired t-test was used to compare mean values between the two groups. Results: The alkaline phosphatase assay showed least cell inhibition for Acemannan and Moringa oleifera (2:1) as 4.45% and osteoblastic differentiation as 0.328 at 540 nm. Titamium disc coated with hydrogel of Acemannan and Moringa oliefera and seeded with Human MSC shows increased proliferation of osteoblast cells.Compare to study group implants, control group showed no new bone formation. Conclusions: Hydrophilic implant surface showed new bone formation with increased bone to implant contact.There was absent of degenerative changes, necrotic changes, fibrosis, and inflammation at the new BIC.

Objective: It is well established that the liver-specific miR-122, a bona fide tumor suppressor, plays a critical role in lipid homeostasis. However, its role, if any, in amino acid metabolism has not been explored. Since glutamine (Gln) is a critical energy and anaplerotic source for mammalian cells, we assessed Gln metabolism in control wild type (WT) mice and miR-122 knockout (KO) mice by stable isotope resolved metabolomics (SIRM) studies. Methods: Six-to eight-week-old WT and KO mice and 12- to 15-month-old liver tumor-bearing mice were injected with [U–13C5,15N2]-L-Gln, and polar metabolites from the liver tissues were analyzed by nuclear magnetic resonance (NMR) imaging and ion chromatography-mass spectrometry (IC-MS). Gln-metabolism was also assessed in a Gln-dependent hepatocellular carcinoma (HCC) cell line (EC4). Expressions of glutaminases (Gls and Gls2) were analyzed in mouse livers and human primary HCC samples. Results: The results showed that loss of miR-122 promoted glutaminolysis but suppressed gluconeogenesis in mouse livers as evident from the buildup of 13C- and/or 15N-Glu and decrease in glucose-6-phosphate (G6P) levels, respectively, in KO livers. Enhanced glutaminolysis is consistent with the upregulation of expressions of Gls (kidney-type glutaminase) and Slc1a5, a neutral amino acid transporter in KO livers. Both Gls and Slc1a5 were confirmed as direct miR-122 targets by the respective 3′-UTR-driven luciferase assays. Importantly, expressions of Gls and Slc1a5 as well as glutaminase activity were suppressed in a Gln-dependent HCC (EC4) cell line transfected with miR-122 mimic that resulted in decreased 13C-Gln, 13C-á-ketoglutarate, 13C-isocitrate, and 13C-citrate levels. In contrast, 13C-phosphoenolpyruvate and 13C-G6P levels were elevated in cells expressing ectopic miR-122, suggesting enhanced gluconeogenesis. Finally, The Cancer Genome Atlas—Liver Hepatocellular Carcinoma (TCGA-LIHC) database analysis showed that expression of GLS is negatively correlated with miR-122 in primary human HCCs, and the upregulation of GLS RNA is associated with higher tumor grade. More importantly, patients with higher expressions of GLS or SLC1A5 in tumors exhibited poor survival compared with those expressing lower levels of these proteins. Conclusions: Collectively, these results show that miR-122 modulates Gln metabolism both in vitro and in vivo, implicating the therapeutic potential of miR-122 in HCCs that exhibit relatively high GLS levels. Keywords: Glutaminase, Glutaminolysis, Gluconeogenesis, Krebs cycle, miRNA-122, miR-122, SIRM, Slc1a5

Congo red (CR) is a toxic azo dye with a complex structure which represents a serious ecotoxicological hazards for aquatic bodies. The present study was aimed to synthesis of metal oxide nanoparticles by applying novel approaches and explore their role in degradation and decolourization of synthetic dye i.e. CR. Zinc oxide (ZnO) and zinc-copper oxides (ZnO/CuO) composite were prepared by the modest chemical co-precipitation process through calcined over 400 °C for 4 h. The acquired materials were characterized by XRD, EDX, SEM, HRTEM, BET, and UV-Visible spectrophotometer. Further, the optimized materials were opted for photodegradation of toxic CR under irradiation of visible light. The experiment demonstrated that ZnO and ZnO/CuO composite can degrade 25% and 95% of CR dye, respectively. ZnO/CuO composite showed better photocatalytic decolorization of CR dye and followed first order kinetics. The result of this study will be helpful in understanding the mechanism of CR degradation through composite materials and help in the development of an efficient technique for degradation and decolourization of CR containing industrial wastewater.

ABSTRACT: Purpose: The radiation oncology workforce in the United States is comparatively less diverse than the U.S. population and U.S. medical school graduates. Workforce diversity correlates with higher quality care and outcomes. The purpose of this study was to determine whether student members of the American Society for Radiation Oncology (ASTRO) are any more diverse than resident members-in-training using the recently established medical student membership category. Methods and Materials: Self-reported sex, race and Hispanic ethnicity, medical school, and degree(s) earned for all medical students (n = 268) and members-in-training (n = 713) were collected from the ASTRO membership database. International members were excluded. The χ2 test was used to assess for differences between subgroups. Results: Compared with members-in-training, student members were more likely to be female (40.0% vs 31.5%, P = .032), black or African American (10.7% vs 4.8%, P = .009), candidates for or holders of a DO rather than MD degree (5.2% vs 1.5%, P = .002), and from a U.S. medical school that is not affiliated with a radiation oncology residency program (30.5% vs 20.9%, P = .001). There was no significant difference in self-reported Hispanic ethnicity (7.3% vs 5.4%, P = .356). There were no indigenous members in either category assessed. Conclusions: Medical student members of ASTRO are more diverse in terms of black race, female sex, and osteopathic training, though not in terms of Hispanic ethnicity or nonmultiracial indigenous background, than the members-in-training. Longitudinal engagement with these students and assessment of the factors leading to specialty retention versus attrition may increase diversity, equity, and inclusion in radiation oncology.

The annual meeting of the American Society of Clinical Oncology is the largest multidisciplinary oncology-focused conference in the world. With more than 4900 total abstracts in 2021 alone, it is difficult for individuals to evaluate all the results. This article presents a review of 32 selected abstracts across all disease sites, focusing on those of greatest relevance to radiation oncologists.

Summary: Talaromycosis (penicilliosis) is an invasive mycosis that is endemic in tropical and subtropical Asia. Talaromycosis primarily affects individuals with advanced HIV disease and other immunosuppressive conditions, and the disease disproportionally affects people in low-income and middle-income countries, particularly agricultural workers in rural areas during their most economically productive years. Approximately 17 300 talaromycosis cases and 4900 associated deaths occur annually. Talaromycosis is highly associated with the tropical monsoon season, when flooding and cyclones can exacerbate the poverty-inducing potential of the disease. Talaromycosis can present as localised or disseminated disease, the latter causing cutaneous lesions that are disfiguring and stigmatising. Despite up to a third of diagnosed cases resulting in death, talaromycosis has received little attention and investment from regional and global funders, policy makers, researchers, and industry. Diagnostic and treatment modalities remain extremely insufficient, however control of talaromycosis is feasible with known public health strategies. This Viewpoint is a global call for talaromycosis to be recognised as a neglected tropical disease to alleviate its impact on susceptible populations.

Background: Mandatory Day 2 and Day 8 PCR testing and variant sequencing of international arrivals has been recently introduced by the UK Government to mitigate against cross-border transmission of high-risk SARS-CoV-2 variants. Methods: SARS-CoV-2 testing and sequencing combines TaqPath CE-IVD COVID-19 RT-PCR with Ion AmpliSeq SARS-CoV-2 Next Generation Sequencing Assay. Retrospective analysis of test trending data was performed from initiation of testing on the 11th March through to the 14th April 2021. Findings: During this time interval, 203,065 SARS-CoV-2 PCR tests were performed, with 3,855 samples testing positive, giving a prevalence of 1.9%. In total 1,913 SARS-CoV-2 genomes were sequenced from positive cases with Ct values 60 with a single dose to 83% in

Purpose: This systematic review was done to find the patients oral health-related quality of life (OHRQoL) and satisfaction with implant supported overdentures (IODs) when compared to conventional complete dentures (CCDs). Materials and methods: To identify suitable literature, an electronic search was performed using Medline/PubMed and Cochrane databases. Manual search of Prosthodontics, Gerodontology and journals related to dental implants were also done. Articles published in English and articles whose abstract is available in English were included. The search was focused on patient's oral health-related quality of life and satisfaction with IODs when compared to CCDs.Titles and abstracts were screened, and literature that fulfilled the inclusion criteria was selected for a full-text reading. Results: Initial literature search resulted in 1803 papers, 1779 were excluded after screenings of the abstracts by the reviewers which resulted in 24 studies. 5 studies were further excluded due to not fulfilling the inclusion criteria, 2 additional articles included after hand searching, resulting in total 21 articles in systematic review. The result suggests that mandibular CCDs had less retention as compared to maxillary conventional dentures CCDs, which improved drastically with IODs and provides a better oral health-related quality of life and satisfaction to the patients. Conclusion: Retention, stability, comfort, speech and chewing efficiency improved drastically with IODs, with enhanced patient's satisfaction and a better OHRQoL. Patients reported more satisfaction and OHRQoL with mandibular IOD when compared CCDs.

Background: Rapid increase of products containing titanium leads to the increases in percutaneous and permucosal exposure of populations to the titanium. Purpose: Evaluate the various material compositions in five commercially available dental implant systems and correlate the obtained material contents with allergic conditions seen with implants. Material and methods: A total of 25 implant, with 5 samples each in 5 groups of commercially available dental implants (MKIII, Myriad, Nobel Replace, MIS and Alpha Dent) were used in the study. Positive Material Identification (PMI) testing was done to analyse the amount of different metals (percentage by mass) present in the dental implants. Results: Highest titanium content, 99.47% by mass was found in sample 2 (Myriad) and least, 89.04% by mass in sample 5(Alpha dent). Nickel was found only in sample 5 (Alpha dent) in 0.079% by mass and zinc in sample 4 (MIS) in0.084% by mass, chromium was found in sample 1 (MK III) in 0.263% by mass and in sample 2 in0.273% by mass. Conclusions: Implant composition should be made mandatory to be disclosed on the implant packet and before implant placement patch test for the allergen present in the particular implant can be done for the patient's health benefit and long term clinical success of dental implants.

Objective: To assess the effect of nationwide lockdown and its associated repercussion on the self-care management of Type 2 Diabetes Mellitus (T2D). Methods: Response from 1406 diabetic patients was collected against a 16 item questionnaire. Data was collected on diabetic self-management practices, behavioral aspects, psychological implications, drug availability and awareness towards the pandemic. Emphasis was on choices made by patients in the absence of guidance from physicians and impact of stress and blood sugar levels on other variables. The data was analyzed using Chi-square tests at P

The purpose of this research was to assess the existing variations in the residency training resources among radiation oncology (RO) residency programs in the United States. We queried each residency program website and Fellowship Residency Electronic Interactive Data Access System website (www.freida.ama-assn.org) to obtain information on faculty and available treatment modalities. The data were continuously updated, most recently as of April 30, 2019. A total of 94 RO residency programs were identified during the academic year 2018-2019, and data were collected. The median number of attending physicians was 13 (range, 4 -71). The median number of physicists and biologists were 9 and 3, respectively. The conventional techniques, including 3 dimensional conformal radation therapy, intensity modulated radiation therapy, electron therapy, and stereotactic body radiation therap/stereotactic radiosurgery, were available in all residency programs. In terms of specialized external beam radiation therapy machines, gamma knife, CyberKnife, and magnetic resonance imaging (MRI) linear accelerator were available in 49 (52%), 21(22%), and 7 (8%) programs, respectively. Only 19 programs (20%) had in-house proton therapy availability; however, 37 programs (39%) offered proton therapy training via resident rotation at an affiliated institution. Prostate, gynecologic, and breast brachytherapy were available in 81 (86%), 82 (87%), and 58 (62%) programs, respectively. Eighty-one (86%) programs reported to have high dose rate, and only 20 (21%) programs had low dose rate brachytherapy. Our study found that marked variations exist among RO residency programs in the United States during academic year 2018-2019 and will serve as a baseline for future intervention.

Purpose: The emergence of the coronavirus disease (COVID-19) global pandemic has led to a significant shift in the delivery of health care, including an explosive growth of telemedicine services. This reverberated in the field of radiation oncology, with a recent American Society for Radiation Oncology (ASTRO) nationwide survey reporting 89% of surveyed clinics began to offer telemedicine programs to patients because of the pandemic. However, this survey did not study the perceptions and experiences of those clinicians delivering telemedicine services. Methods and Materials: We investigated through a national physician survey the merits and limitations of radiation oncology tele-consultations. An anonymous web-based survey was distributed using SurveyMonkey (www.surveymonkey.com) via email. Results: Seventy six respondents (16.1% overall response rate) completed the survey, with broad representation from both academic and community-based practices. Many respondents agreed that transitioning to tele-consultations was a needed step given the emergence of the pandemic, despite most having never previously offered this service. Despite many radiation oncologists having little prior experience with tele-consultations, a majority were satisfied in being able to explain the details of a medical diagnosis, provide results of imaging and bloodwork, and discuss recommendations around radiation treatments through this format. Nearly half of the respondents agreed that tele-consultations felt impersonal, with the inability to complete physical examinations noted as a contributor to the impersonality. Nevertheless, respondents still agreed that telemedicine will play an important role going forward, and almost 90% agreed that they would offer tele-consultations even after the pandemic has resolved.

Elevation of pressure within tightly bound myofascial compartments has detrimental consequences if not treated promptly, leading to a loss of circulation, ischemia, myonecrosis, nerve damage, and limb loss. They are commonly seen in the distal upper and lower extremities; however, compartment syndrome of the hand is rarely encountered and prompt recognition can prevent permanent damage and tissue loss. This case study presents a complicated case of compartment syndrome of the hand and discusses the interrelationship between compartment syndrome and rhabdomyolysis. An emphasis is placed on pathophysiology of this relationship to allow a better understanding of the imaging features as well as early clinical recognition of compartment syndrome. Magnetic resonance imaging findings are specifically discussed as it remains the best imaging tool to evaluate the extent of the damage and surgical planning.

Summary: Human erythropoiesis serves as a paradigm of physiologic cellular differentiation. This process is also of considerable interest for better understanding anemias and identifying new therapies. Here, we apply deep transcriptomic and accessible chromatin profiling to characterize a faithful ex vivo human erythroid differentiation system from hematopoietic stem and progenitor cells. We reveal stage-specific transcriptional states and chromatin accessibility during various stages of erythropoiesis, including 14,260 differentially expressed genes and 63,659 variably accessible chromatin peaks. Our analysis suggests differentiation stage-predominant roles for specific master regulators, including GATA1 and KLF1. We integrate chromatin profiles with common and rare genetic variants associated with erythroid cell traits and diseases, finding that variants regulating different erythroid phenotypes likely act at variable points during differentiation. In addition, we identify a regulator of terminal erythropoiesis, TMCC2, more broadly illustrating the value of this comprehensive analysis to improve our understanding of erythropoiesis in health and disease. : Ludwig et al. chart the dynamic transcriptional and chromatin landscapes as hematopoietic stem and progenitor cells differentiate into mature red blood cells. This multi-omic profiling reveals dynamic transcription factor activities and human genetic variation that modulate this process. Keywords: erythropoiesis, red blood cell, chromatin accessibility, transcriptomics, GWAS, human genetics, hematopoiesis

Candida auris is an emerging multidrug resistant yeast that causes nosocomial fungaemia and deep-seated infections. Notably, the emergence of this yeast is alarming as it exhibits resistance to azoles, amphotericin B and caspofungin, which may lead to clinical failure in patients. The multigene phylogeny and amplified fragment length polymorphism typing methods report the C. auris population as clonal. Here, using whole genome sequencing analysis, we decipher for the first time that C. auris strains from four Indian hospitals were highly related, suggesting clonal transmission. Further, all C. auris isolates originated from cases of fungaemia and were resistant to fluconazole (MIC >64 mg/L).