Emotion detection from handwriting and drawing samples using an attention-based transformer model.

Emotion detection (ED) involves the identification and understanding of an individual's emotional state through various cues such as facial expressions, voice tones, physiological changes, and behavioral patterns. In this context, behavioral analysis is employed to observe actions and behaviors for emotional interpretation. This work specifically employs behavioral metrics like drawing and handwriting to determine a person's emotional state, recognizing these actions as physical functions integrating motor and cognitive processes. The study proposes an attention-based transformer model as an innovative approach to identify emotions from handwriting and drawing samples, thereby advancing the capabilities of ED into the domains of fine motor skills and artistic expression. The initial data obtained provides a set of points that correspond to the handwriting or drawing strokes. Each stroke point is subsequently delivered to the attention-based transformer model, which embeds it into a high-dimensional vector space. The model builds a prediction about the emotional state of the person who generated the sample by integrating the most important components and patterns in the input sequence using self-attentional processes. The proposed approach possesses a distinct advantage in its enhanced capacity to capture long-range correlations compared to conventional recurrent neural networks (RNN). This characteristic makes it particularly well-suited for the precise identification of emotions from samples of handwriting and drawings, signifying a notable advancement in the field of emotion detection. The proposed method produced cutting-edge outcomes of 92.64% on the benchmark dataset known as EMOTHAW (Emotion Recognition via Handwriting and Drawing).

Transvenous endocardial pacing with SelectSecure™ 3830 lead in pediatric patients: case series of two infants and a literature review.

BACKGROUND: The SelectSecure™ 3830 lead is an innovative, lumenless, and thin active fixed lead with a nonretractable screw-in tip and a diameter of 4.1 Fr, making it the thinnest pacing lead available. Its high anti-extrusion properties and durability have shown favorable outcomes in cardiac pacing, especially in pediatric patients. The superfine design and easy implantation of the lead have rendered it a preferred choice in children, particularly in cases of congenital heart disease. CASE PRESENTATION: This case series presents two infant patients who underwent transvenous endocardial pacing using the SelectSecure™ 3830 lead, along with a comprehensive literature review on the topic. The study followed the patients for 5 years and 3 years, respectively, and observed stable pacing parameters, indicating a positive therapeutic outcome and safety. This article discusses the optimal age and body shape for transvenous lead implantation in infants and highlights the advantages and disadvantages of endocardial and epicardial pacing approaches. Although endocardial pacing offers several benefits such as minimal trauma, short hospital stay, and longer battery life, it may not be suitable for intracardiac shunts, and venous occlusion remains a concern. On the other hand, epicardial pacing may be considered for children with challenging endocardial access but comes with higher risk of lead failure and coronary artery compression. This study emphasizes the importance of careful follow-up in pediatric patients with pacing, as lead failure can occur in young patients owing to growth and development, leading to syncope and battery depletion. The article also underscores the significance of selecting the appropriate pacing location to minimize the impact of cardiac function, with right ventricular septal pacing emerging as a preferable option. CONCLUSIONS: The SelectSecure™ 3830 lead presents a promising solution for transvenous endocardial pacing in pediatric patients with high degree atrioventricular block and bradycardia, ensuring safe and effective pacing as they grow and develop.

Tuberculous Septic Arthritis of the Hip Following the Incision and Drainage of a Groin Abscess: A Case Report.

Tuberculosis of the hip is a relatively rare type of septic arthritis that is seldom seen in the developed world today. While pyogenic septic arthritis may present with clear features that help in early diagnosis and treatment, many of these features are absent or overlap significantly with tuberculous arthritis, making the diagnosis a clinical challenge. Here, we present a case of tuberculous septic arthritis seen in our clinic following the surgical incision and drainage of a groin abscess with minimal hip symptoms. We discuss the therapeutic approach for the patient and briefly review other reported cases of tuberculous septic arthritis in the literature.

Association of Fracture Location and Pattern With Nonunion or Malunion in Tibia Fractures Managed With Intramedullary Nailing: A Retrospective Study.

Background and objective Extra-articular fractures of the tibia are common orthopedic injuries that are frequently treated with rigid intramedullary nailing. Fracture location and pattern may increase the risk of nonunion or malunion in fractures managed with intramedullary nails. This study aimed to assess the relationship between fracture pattern and location with malunion and nonunion. The primary objective was to evaluate the influence of fracture location and pattern on adverse clinical outcomes such as nonunion, delayed union, and malunion in tibial shaft fractures that are treated operatively with rigid intramedullary nails. Methodology This was a retrospective cross-sectional study conducted on patients operated in a tertiary care center in the Kingdom of Bahrain. The study included patients who sustained tibia shaft fractures and were subsequently operated with intramedullary of the tibia. The primary endpoint was the rate of adverse outcomes associated with fracture patterns. Fracture characteristics were to determine which fracture patterns healed well with intramedullary nailing and which fractures ended up with malunion or nonunion and would likely benefit from additional measures to augment the nail fixation and help encourage union. Results One hundred and eighty-nine patients were included in the study. The level of associated fibula fracture was significantly associated with an increased risk of nonunion and malunion (P = 0.0034, P = 0.001). The presence of a concomitant distal fibula fracture in association with tibia fractures increased the odds of nonunion (odds ratio [OR] = 4.871, P = 0.033, confidence interval [CI] = 1.133-20.948). Conclusions The level and pattern of some tibia and fibula fractures were associated with nonunion, malunion, and delayed union. Further studies with more robust follow-up are needed to examine these findings in greater detail.

Classification of Parkinson's Disease in Patch-Based MRI of Substantia Nigra.

Parkinson's disease (PD) is a chronic and progressive neurological disease that mostly shakes and compromises the motor system of the human brain. Patients with PD can face resting tremors, loss of balance, bradykinesia, and rigidity problems. Complex patterns of PD, i.e., with relevance to other neurological diseases and minor changes in brain structure, make the diagnosis of this disease a challenge and cause inaccuracy of about 25% in the diagnostics. The research community utilizes different machine learning techniques for diagnosis using handcrafted features. This paper proposes a computer-aided diagnostic system using a convolutional neural network (CNN) to diagnose PD. CNN is one of the most suitable models to extract and learn the essential features of a problem. The dataset is obtained from Parkinson's Progression Markers Initiative (PPMI), which provides different datasets (benchmarks), such as T2-weighted MRI for PD and other healthy controls (HC). The mid slices are collected from each MRI. Further, these slices are registered for alignment. Since the PD can be found in substantia nigra (i.e., the midbrain), the midbrain region of the registered T2-weighted MRI slice is selected using the freehand region of interest technique with a 33 × 33 sized window. Several experiments have been carried out to ensure the validity of the CNN. The standard measures, such as accuracy, sensitivity, specificity, and area under the curve, are used to evaluate the proposed system. The evaluation results show that CNN provides better accuracy than machine learning techniques, such as naive Bayes, decision tree, support vector machine, and artificial neural network.

Coronary Artery Stent Dislodgement and Loss in the Bloodstream: A Case Report and Management Options.

BACKGROUND Coronary stent dislodgement is rare but carries serious complications like thrombosis, myocardial infarction, disruption of the systemic circulation, and coronary dissection, which can lead to sudden death. Thus, rapid evaluation and intervention are needed to restore blood flow to vital organs. CASE REPORT A 46-year-old woman with no relevant past medical history except for smoking, presented to the Emergency Department (ED) with left-sided chest pain. The physical exam was unremarkable. EKG showed ST segment elevation, and troponin was 4.03. She underwent cardiac catheterization, which showed 100% occlusion of the left anterior descending coronary artery (LAD). A drug-eluting stent (DES) was placed. Later, she had chest pain similar to the initial episode. EKG showed 1-mm elevation at ST segment in leads V1 and V2 and T wave inversion in leads V2, V3, V4, and V5. She underwent a repeat heart catheterization, which revealed a dissection in the middle LAD distal to the initial stent placement. She was treated with another stent overlapping the proximal stent. While attempting to cross the proximal stent, the stent came off the balloon, slipped from the wire, and went down into the descending aorta. CONCLUSIONS Coronary artery stent dislodgement is a rare event that can lead to significant complications during PCI. Patient restlessness and small-sized, severely angulated, and previously stented coronary arteries are associated risk factors. The main treatment option is stent retrieval, either surgically or using other available techniques. If retrieval of the stent is impossible, crushing it against the blood vessel wall could be considered.

Electrospun Biomimetic Nanofibrous Scaffolds: A Promising Prospect for Bone Tissue Engineering and Regenerative Medicine.

Skeletal-related disorders such as arthritis, bone cancer, osteosarcoma, and osteoarthritis are among the most common reasons for mortality in humans at present. Nanostructured scaffolds have been discovered to be more efficient for bone regeneration than macro/micro-sized scaffolds because they sufficiently permit cell adhesion, proliferation, and chemical transformation. Nanofibrous scaffolds mimicking artificial extracellular matrices provide a natural environment for tissue regeneration owing to their large surface area, high porosity, and appreciable drug loading capacity. Here, we review recent progress and possible future prospective electrospun nanofibrous scaffolds for bone tissue engineering. Electrospun nanofibrous scaffolds have demonstrated promising potential in bone tissue regeneration using a variety of nanomaterials. This review focused on the crucial role of electrospun nanofibrous scaffolds in biological applications, including drug/growth factor delivery to bone tissue regeneration. Natural and synthetic polymeric nanofibrous scaffolds are extensively inspected to regenerate bone tissue. We focused mainly on the significant impact of nanofibrous composite scaffolds on cell adhesion and function, and different composites of organic/inorganic nanoparticles with nanofiber scaffolds. This analysis provides an overview of nanofibrous scaffold-based bone regeneration strategies; however, the same concepts can be applied to other organ and tissue regeneration tactics.

Palbociclib plus letrozole as treatment for postmenopausal women with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer for whom letrozole therapy is deemed appropriate: An expanded access study in Australia and India.

AIM: Palbociclib was approved in the United States in 2015 to treat estrogen receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). This study evaluated outcomes and safety in patients treated with palbociclib in Australia and India with hormone receptor-positive (HR+)/HER2- ABC before palbociclib became commercially available. METHODS: Postmenopausal women (≥18 years) with HR+/HER2- ABC who were appropriate candidates for letrozole therapy received palbociclib 125 mg once daily for 21 days followed by 7 days off, and letrozole 2.5 mg once daily (continuous). Safety, tumor response, and patient-reported outcomes (Australian cohort) were evaluated. RESULTS: In total, 252 patients received palbociclib plus letrozole (Australia, n = 152; India, n = 100). More patients in the Australian versus Indian cohort had received prior chemotherapy (advanced/metastatic setting: 45.9% vs. 32.0%), endocrine therapy (advanced/metastatic setting: 63.2% vs. 54.3%), and advanced/metastatic therapies (61.8% vs. 31.0%). The most frequently reported all-grade palbociclib-related treatment-emergent adverse events were neutropenia (66.7%), fatigue (35.3%), and stomatitis (26.6%); grade 3/4 neutropenia was reported as palbociclib-related in 62.7% of patients. Febrile neutropenia was reported in six patients (2.4%). Eight patients (3.2%) discontinued because of an adverse event. The objective response rate was 19.4% (95% CI, 14.7%-24.9%) overall and 2.3% in Australian patients with ≥2 lines of prior therapy for metastatic disease. Patient-reported quality of life scores were maintained throughout the study. CONCLUSIONS: In an expanded access setting in Australia and India, palbociclib plus letrozole was well tolerated in patients with HR+/HER2- ABC, with a safety profile consistent with previous reports.

Integrated phosphorus nutrient sources improve wheat yield and phosphorus use efficiency under sub humid conditions.

Majority of Pakistani soils are deficient in phosphorus. Phosphorus is usually applied in form of synthetic fertilizer. However integrated use of P from synthetic and organic sources can be more profitable and beneficial on sustainable basis. Field trials were conducted at research farm University of Poonch, Rawalakot, AJK, Pakistan for two consecutive years to check the comparative effects of synthetic fertilizer and organic manures applied alone and in combinations on the phosphorus use efficiency (PUE), wheat yield and yield components. Shafaq-06 cultivar of wheat was used as test cultivar. Ten treatments were included: (I) Control (P0) without application of fertilizer; (II) SSP @ 60 kg/ha (P60SSP); (III) SSP @ 90 kg/ha (P90SSP); (IV) SSP @ 120 kg/ha (P120SSP); (V) PM @60 kg/ha (P60PM); (VI) PM @90 kg/ha (P90PM); (VII) PM @120 kg/ha (P120PM); (VIII) SSP @30 kg/ha + PM @30 kg/ha (P30SSP+30PM); (IX) SSP @45 kg/ha + PM @45 kg/ha (P45SSP+45PM); (X) SSP @60 kg/ha + PM @60 kg/ha (P60SSP+60PM) which were laid out under the Randomized Complete Block Design. Significantly higher values for yield of grain (2397 kg/ha) was recorded with PM + SSP @ 60 kg P2O5 ha-1 each. Likewise, FPUE, PIR of wheat and AFPUE was quite higher with combined use of PM and SSP i.e. P60SSP+60PM treatment. Additionally, increase in PUE, wheat yield and yield components associated with combined treated plot would help to minimize the use of high cost synthetic mineral fertilizers and represents an environmentally and agronomically sound management strategy.

Interference of horse purslane (Trianthema portulacastrum L.) and other weeds affect yield of autumn planted maize (Zea mays L.).

To assess comparative losses of Trianthema portulacastrum (HP) relative to other weeds, the experiment was set during consecutive summer seasons 2018 and 2019 at the Research Farm MNS-University of Agriculture, Multan, Pakistan. Experiment consisted three replications which were laid out under randomized complete block design. Experiment consisted of ten treatments viz: weeds free (whole season), HP free till 20 Days after emergence (DAE), HP free till 40 DAE, HP free till 60 DAE, all weeds free 20 DAE, all weeds free 40 DAE, all weeds free 60 DAE, weedy check (all weeds), weedy check except HP and weedy check containing only HP. During 2018 in all weeds weedy check, maximum HP relative density (33.33%) was observed while in 2019, plot where weeds were controlled from growing till 20 DAE showed (80%) relative density at 30 DAE. HP maximum frequency (66.67%, 77.78%) and relative frequency (66%, 100%) was recorded at 45 DAE in plots where HP was kept controlled till 20 DAE and all weeds kept controlled till 20 DAE, respectively. Maximum number of grains per cob (738, 700.68), 1000 grain weight (306.66, 271.51 g) and grain yield (6150, 8015 kg hec-1) were recorded in plots which were kept all weed free till 60 DAE. As the competition period of weeds increased over 40 DAE, it substantially reduced yield of maize. Keeping the plots HP free till 40 DAE in the maize fields with HP as the major dominating weed, likely increase in maize grain yield is up to 30% compared to the fields where HP left un attended throughout the growing season. However, if maize field is infested with a mix of weeds with more than one dominating weeds including HP, compared to weedy situation the whole season, 30% higher grain yield can be obtained if all weeds are kept controlled till 40 DAE. Hence it can be concluded that whether the farmers face heavy HP infestation only or the mix of weeds as dominating weeds, in either case farmer should control weeds within first 40 days in maize field for better grain yield.

Development of Potent PfCLK3 Inhibitors Based on TCMDC-135051 as a New Class of Antimalarials.

The protein kinase PfCLK3 plays a critical role in the regulation of malarial parasite RNA splicing and is essential for the survival of blood stage Plasmodium falciparum. We recently validated PfCLK3 as a drug target in malaria that offers prophylactic, transmission blocking, and curative potential. Herein, we describe the synthesis of our initial hit TCMDC-135051 (1) and efforts to establish a structure-activity relationship with a 7-azaindole-based series. A total of 14 analogues were assessed in a time-resolved fluorescence energy transfer assay against the full-length recombinant protein kinase PfCLK3, and 11 analogues were further assessed in asexual 3D7 (chloroquine-sensitive) strains of P. falciparum parasites. SAR relating to rings A and B was established. These data together with analysis of activity against parasites collected from patients in the field suggest that TCMDC-135051 (1) is a promising lead compound for the development of new antimalarials with a novel mechanism of action targeting PfCLK3.

Adapting care for older cancer patients during the COVID-19 pandemic: Recommendations from the International Society of Geriatric Oncology (SIOG) COVID-19 Working Group.

The COVID-19 pandemic poses a barrier to equal and evidence-based management of cancer in older adults. The International Society of Geriatric Oncology (SIOG) formed a panel of experts to develop consensus recommendations on the implications of the pandemic on several aspects of cancer care in this age group including geriatric assessment (GA), surgery, radiotherapy, systemic treatment, palliative care and research. Age and cancer diagnosis are significant predictors of adverse outcomes of the COVID-19 infection. In this setting, GA is particularly valuable to drive decision-making. GA may aid estimating physiologic reserve and adaptive capability, assessing risk-benefits of either providing or temporarily withholding treatments, and determining patient preferences to help inform treatment decisions. In a resource-constrained setting, geriatric screening tools may be administered remotely to identify patients requiring comprehensive GA. Tele-health is also crucial to ensure adequate continuity of care and minimize the risk of infection exposure. In general, therapeutic decisions should favor the most effective and least invasive approach with the lowest risk of adverse outcomes. In selected cases, this might require deferring or omitting surgery, radiotherapy or systemic treatments especially where benefits are marginal and alternative safe therapeutic options are available. Ongoing research is necessary to expand knowledge of the management of cancer in older adults. However, the pandemic presents a significant barrier and efforts should be made to ensure equitable access to clinical trials and prospective data collection to elucidate the outcomes of COVID-19 in this population.

Validation of the protein kinase PfCLK3 as a multistage cross-species malarial drug target.

The requirement for next-generation antimalarials to be both curative and transmission-blocking necessitates the identification of previously undiscovered druggable molecular pathways. We identified a selective inhibitor of the Plasmodium falciparum protein kinase PfCLK3, which we used in combination with chemogenetics to validate PfCLK3 as a drug target acting at multiple parasite life stages. Consistent with a role for PfCLK3 in RNA splicing, inhibition resulted in the down-regulation of more than 400 essential parasite genes. Inhibition of PfCLK3 mediated rapid killing of asexual liver- and blood-stage P. falciparum and blockade of gametocyte development, thereby preventing transmission, and also showed parasiticidal activity against P. berghei and P. knowlesi Hence, our data establish PfCLK3 as a target for drugs, with the potential to offer a cure-to be prophylactic and transmission blocking in malaria.

Blood-based microRNAs as diagnostic biomarkers to discriminate localized prostate cancer from benign prostatic hyperplasia and allow cancer-risk stratification.

Prostate cancer (PCa) is the second most diagnosed malignancy, and the leading cause of cancer-associated mortality among males. Prostate-specific antigen (PSA) has long been used for the detection of PCa. However, PSA levels increase in PCa and benign prostatic hyperplasia (BPH), and are associated with a poor disease outcome. Circulating microRNAs (miRNAs) have been determined to be highly stable in the circulation, and could be utilized as biomarkers to improve disease diagnosis and management. In the present study, the effectiveness of four PCa-associated miRNAs in the discrimination of PCa from BPH and the risk-stratification of PCa was assessed. The study included 100 participants: 35 patients with localized PCa, 35 patients with BPH and 30 healthy subjects. Patients with PCa were categorized based on their tumor stage (T), PSA level and Gleason score (GS) into low-(T 1/2, PSA <10 ng/ml or GS ≤7) and high-risk groups (T 3/4, PSA >20 ng/ml or GS ≥8). Reverse transcription-quantitative polymerase chain reaction was employed to assess the miRNA expression in peripheral blood samples. Significantly reduced expression of miR-15a, miR-126, miR-192 and miR-377 was observed in patients with PCa compared with patients with BPH and healthy subjects. In addition, the expression of the four miRNAs was lower in high-risk PCa patients than in low-risk PCa patients, with miR-126 being the most downregulated. The expression of the four miRNAs was also significantly and independently associated with PCa. Receiver operating characteristic curve analysis revealed a significant ability of the miRNAs to distinguish patients with PCa from those with BPH, patients with PCa from controls and low-risk PCa from high-risk PCa. These data suggested that expression of these miRNAs in the blood circulation may be promising, non-invasive biomarkers for the early detection of localized PCa, and for PCa risk stratification. Further validations of the clinical implementation of these results are warranted in a larger cohort.

Evaluation of response from axitinib per Response Evaluation Criteria in Solid Tumors versus Choi criteria in previously treated patients with metastatic renal cell carcinoma.

BACKGROUND: Axitinib, a selective and potent tyrosine kinase inhibitor of vascular endothelial growth factor receptors, was available to patients from Canada and Australia, prior to regulatory approval of axitinib in these countries, for treatment of clear-cell metastatic renal cell carcinoma (mRCC) after failure of one prior systemic regimen. METHODS: This single-arm, open-label study of axitinib evaluated the efficacy, safety, and quality of life (QoL) in patients with mRCC whose disease progressed after one prior systemic first-line regimen. Primary objective was objective response rate evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) and Choi criteria. Progression-free survival, overall survival, safety, and QoL were secondary end points. Due to the small study size, analyses comprised of descriptive statistics. RESULTS: Fifteen patients were recruited, five from Canada and ten from Australia, over a limited recruitment period. Thirteen patients received sunitinib as prior therapy. All patients had clear-cell carcinoma, eleven had prior nephrectomy. Liver, lung, and lymph nodes were the most frequent sites of metastases; one patient had brain metastasis. Median time on axitinib was 118.0 days (range: 3.5-645.0 days); estimated survival probability at 12 months was 57.8%. Two (13.3%) patients had objective responses per RECIST versus nine (60.0%) per Choi criteria. Six patients had progressive disease based on RECIST versus three per Choi criteria. Nine (60.0%) events of progression or death occurred by the end of study, and three patients continued to receive the study drug. Fatigue (33%) and diarrhea (20%) were the most common grade ≥3 all-causality, treatment-emergent adverse events. The mean change in European Quality of Life - 5 Dimensions score from baseline to end of treatment was -0.0837. CONCLUSION: The small number of patients and lack of a comparator arm limit the ability to draw definitive conclusions; however, safety and efficacy profiles of axitinib were consistent with reports from previous studies in patients with mRCC, and patients generally maintained QoL. The sizeable difference observed in objective response rate by RECIST versus Choi criteria merits further research.

The prevalence, severity, and correlates of psychological distress and impaired health-related quality of life following treatment for testicular cancer: a survivorship study.

PURPOSE: This study aimed to establish the prevalence, severity, and correlates of psychological distress and impaired generic health-related quality of life (HRQOL) in testicular cancer (TC) survivors. METHODS: Men who had completed active anti-cancer treatment for TC between 6 months and 5 years previously showing no evidence of recurrence were recruited from 14 Australian cancer centers from September 2009 to February 2011. Participants completed a self-report questionnaire measuring demographic, disease, and treatment information, psychological distress (i.e., depression, anxiety, and stress; DASS21), generic health-related quality of life (HRQOL; SF-36v2), TC-specific HRQOL (EORTC QLQ-TC26), coping (MAC), social support (DUFSS), and unmet needs (CaSUN). RESULTS: Of 486 eligible TC survivors, 244 (50.2%) completed the questionnaire. Compared with normative data, TC survivors reported: small but statistically significant increases in mean levels of anxiety and depression; a greater prevalence of moderate to extremely severe anxiety (19%) and depression (20%); and significant deficits to mostly mental aspects of generic HRQOL. The most problematic TC-specific HRQOL issues (e.g., fear of recurrence) were also more mental than physical. In multiple regression analyses, the strongest correlates of psychological distress and impaired generic HRQOL were psychosocial (e.g., helpless/hopeless coping and lower social support) rather than disease or treatment factors. CONCLUSIONS: Generally, TC survivors appear to experience mild psychological distress and HRQOL impairments, while a vulnerable subgroup experience more severe morbidity. IMPLICATIONS FOR CANCER SURVIVORS: There is a need to identify TC survivors at risk of poorer outcomes and for interventions to target the areas of greatest impairment (i.e., psychological distress and mental HRQOL).

Elevated Troponin I in the Absence of Coronary Artery Disease: A Case Report With Review of Literature.

Cardiac troponins are the most sensitive and specific markers of myocardial injury. In fact, the Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction (MI) states that troponins are the preferred cardiac marker for detecting myocardial injury. For the aforementioned reasons, troponin levels are routinely ordered for patients presenting to the emergency department with chest pain, dyspnea, syncope, or any other possible presentations of MI. While troponin levels do reflect the extent of myocardial damage, they do not necessarily indicate myocardial ischemia in a subset of patients. Elevated troponin levels can be due to a wide array of mechanisms in the absence of myocardial ischemia and injury. Thus, relying solely on troponin levels, in the presence of a normal electrocardiogram (ECG), to diagnose myocardial ischemia can lead to unnecessary and expensive invasive testing. It is therefore important for the clinician to keep in mind the varying causes of troponin elevations in order to provide the highest value care to the patient. We present a case and review of literature regarding patients who present with elevated troponin levels in the absence of any coronary artery disease.

Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion.

Our understanding of the key phosphorylation-dependent signalling pathways in the human malaria parasite, Plasmodium falciparum, remains rudimentary. Here we address this issue for the essential cGMP-dependent protein kinase, PfPKG. By employing chemical and genetic tools in combination with quantitative global phosphoproteomics, we identify the phosphorylation sites on 69 proteins that are direct or indirect cellular targets for PfPKG. These PfPKG targets include proteins involved in cell signalling, proteolysis, gene regulation, protein export and ion and protein transport, indicating that cGMP/PfPKG acts as a signalling hub that plays a central role in a number of core parasite processes. We also show that PfPKG activity is required for parasite invasion. This correlates with the finding that the calcium-dependent protein kinase, PfCDPK1, is phosphorylated by PfPKG, as are components of the actomyosin complex, providing mechanistic insight into the essential role of PfPKG in parasite egress and invasion.