Monitoring the world-oldest zoo-housed male giant panda (Ailuropoda melanoleuca): A case-study on pathway utilization.

Habitat use monitoring is necessary for a comprehensive understanding of the biological and psychological requirements of animals under human care, facilitating improved exhibit designs and promoting animal welfare. Current studies focused on the space use of the exhibit while limited studies examined the pathway use of the zoo-housed animals. This study aimed to investigate the habitat use of An An, the world-oldest male giant panda (Ailuropoda melanoleuca) at Ocean Park Hong Kong using a pathway utilization monitoring method. The result showed uneven utilization of pathways favoring the upper area near his den over the lower area which required longer walking in the hilly exhibit. Moreover, the comparisons of walking directions showed a preference for gentle slopes during uphill movement and a favor for steep slopes during downhill movement. Our study also compared the walking distance between uphill and downhill movements and the results showed that An An walked longer distances heading upward than moving downward due to his choice of pathways. Our results are in line with the findings in the wild population, showing a preference for gentle slopes, especially in uphill movement. Our study demonstrated the value of the pathway monitoring technique. Due to its easy and time-effective use, this technique can be incorporated into the care teams' operation, providing valuable information on daily activity (e.g. accessing the walking ability of the aged animals by investigating the pathway use and walking distance) and habitat use. Consequently, the pathway monitoring technique can help improve exhibit designs promoting welfare.

Democratizing Artificial Intelligence Imaging Analysis With Automated Machine Learning: Tutorial.

Deep learning-based clinical imaging analysis underlies diagnostic artificial intelligence (AI) models, which can match or even exceed the performance of clinical experts, having the potential to revolutionize clinical practice. A wide variety of automated machine learning (autoML) platforms lower the technical barrier to entry to deep learning, extending AI capabilities to clinicians with limited technical expertise, and even autonomous foundation models such as multimodal large language models. Here, we provide a technical overview of autoML with descriptions of how autoML may be applied in education, research, and clinical practice. Each stage of the process of conducting an autoML project is outlined, with an emphasis on ethical and technical best practices. Specifically, data acquisition, data partitioning, model training, model validation, analysis, and model deployment are considered. The strengths and limitations of available code-free, code-minimal, and code-intensive autoML platforms are considered. AutoML has great potential to democratize AI in medicine, improving AI literacy by enabling "hands-on" education. AutoML may serve as a useful adjunct in research by facilitating rapid testing and benchmarking before significant computational resources are committed. AutoML may also be applied in clinical contexts, provided regulatory requirements are met. The abstraction by autoML of arduous aspects of AI engineering promotes prioritization of data set curation, supporting the transition from conventional model-driven approaches to data-centric development. To fulfill its potential, clinicians must be educated on how to apply these technologies ethically, rigorously, and effectively; this tutorial represents a comprehensive summary of relevant considerations.

Interdisciplinary Approach to Identify and Characterize COVID-19 Misinformation on Twitter: Mixed Methods Study.

BACKGROUND: Studying COVID-19 misinformation on Twitter presents methodological challenges. A computational approach can analyze large data sets, but it is limited when interpreting context. A qualitative approach allows for a deeper analysis of content, but it is labor-intensive and feasible only for smaller data sets. OBJECTIVE: We aimed to identify and characterize tweets containing COVID-19 misinformation. METHODS: Tweets geolocated to the Philippines (January 1 to March 21, 2020) containing the words coronavirus, covid, and ncov were mined using the GetOldTweets3 Python library. This primary corpus (N=12,631) was subjected to biterm topic modeling. Key informant interviews were conducted to elicit examples of COVID-19 misinformation and determine keywords. Using NVivo (QSR International) and a combination of word frequency and text search using key informant interview keywords, subcorpus A (n=5881) was constituted and manually coded to identify misinformation. Constant comparative, iterative, and consensual analyses were used to further characterize these tweets. Tweets containing key informant interview keywords were extracted from the primary corpus and processed to constitute subcorpus B (n=4634), of which 506 tweets were manually labeled as misinformation. This training set was subjected to natural language processing to identify tweets with misinformation in the primary corpus. These tweets were further manually coded to confirm labeling. RESULTS: Biterm topic modeling of the primary corpus revealed the following topics: uncertainty, lawmaker's response, safety measures, testing, loved ones, health standards, panic buying, tragedies other than COVID-19, economy, COVID-19 statistics, precautions, health measures, international issues, adherence to guidelines, and frontliners. These were categorized into 4 major topics: nature of COVID-19, contexts and consequences, people and agents of COVID-19, and COVID-19 prevention and management. Manual coding of subcorpus A identified 398 tweets with misinformation in the following formats: misleading content (n=179), satire and/or parody (n=77), false connection (n=53), conspiracy (n=47), and false context (n=42). The discursive strategies identified were humor (n=109), fear mongering (n=67), anger and disgust (n=59), political commentary (n=59), performing credibility (n=45), overpositivity (n=32), and marketing (n=27). Natural language processing identified 165 tweets with misinformation. However, a manual review showed that 69.7% (115/165) of tweets did not contain misinformation. CONCLUSIONS: An interdisciplinary approach was used to identify tweets with COVID-19 misinformation. Natural language processing mislabeled tweets, likely due to tweets written in Filipino or a combination of the Filipino and English languages. Identifying the formats and discursive strategies of tweets with misinformation required iterative, manual, and emergent coding by human coders with experiential and cultural knowledge of Twitter. An interdisciplinary team composed of experts in health, health informatics, social science, and computer science combined computational and qualitative methods to gain a better understanding of COVID-19 misinformation on Twitter.

Mitochondrial E3 ubiquitin ligase MARCHF5 controls BAK apoptotic activity independently of BH3-only proteins.

Intrinsic apoptosis is principally governed by the BCL-2 family of proteins, but some non-BCL-2 proteins are also critical to control this process. To identify novel apoptosis regulators, we performed a genome-wide CRISPR-Cas9 library screen, and it identified the mitochondrial E3 ubiquitin ligase MARCHF5/MITOL/RNF153 as an important regulator of BAK apoptotic function. Deleting MARCHF5 in diverse cell lines dependent on BAK conferred profound resistance to BH3-mimetic drugs. The loss of MARCHF5 or its E3 ubiquitin ligase activity surprisingly drove BAK to adopt an activated conformation, with resistance to BH3-mimetics afforded by the formation of inhibitory complexes with pro-survival proteins MCL-1 and BCL-XL. Importantly, these changes to BAK conformation and pro-survival association occurred independently of BH3-only proteins and influence on pro-survival proteins. This study identifies a new mechanism by which MARCHF5 regulates apoptotic cell death by restraining BAK activating conformation change and provides new insight into how cancer cells respond to BH3-mimetic drugs. These data also highlight the emerging role of ubiquitin signalling in apoptosis that may be exploited therapeutically.

Application and impact assessment of an interactive journal club format among endocrinology fellows-in-training in a tertiary hospital academic center: a case study.

Background: The interactive journal club is designed to utilize a new approach in appraising research in order to maximize the benefits of the traditional journal club. In this new approach, the participants are actively involved in a structured process of critical data appraisal rather than just being passive listeners. In this case study, we applied the interactive journal club format and assessed its impact among our endocrinology fellows-in-training. Methods: We conducted four interactive journal club sessions within a four-week span, one per each week via a virtual platform. The 12 participants were the same throughout all sessions. Each session was recorded following informed consent. At the end of all sessions, feedback was obtained, tabulated and compared. Results: Sessions lasted from 59 to 83 minutes (mean, 67.75 minutes). Participants became more active and spontaneous as the sessions progressed. All participants found the format more fun and proactive. This approach allowed more critical thinking and processing of information. Salient features include increased self-esteem and confidence, additional learning from other participants, better retention of information, and utilization in future practice. Conclusions: Traditional approaches are transformed from passive presentations of recent developments in medicine into an interactive discussion while allowing the retention of the spirit and essence of a traditional journal club, as well as exploring new and improved approaches in clinical training and education.

Dynamic reconfiguration of pro-apoptotic BAK on membranes.

BAK and BAX, the effectors of intrinsic apoptosis, each undergo major reconfiguration to an activated conformer that self-associates to damage mitochondria and cause cell death. However, the dynamic structural mechanisms of this reconfiguration in the presence of a membrane have yet to be fully elucidated. To explore the metamorphosis of membrane-bound BAK, we employed hydrogen-deuterium exchange mass spectrometry (HDX-MS). The HDX-MS profile of BAK on liposomes comprising mitochondrial lipids was consistent with known solution structures of inactive BAK. Following activation, HDX-MS resolved major reconfigurations in BAK. Mutagenesis guided by our HDX-MS profiling revealed that the BCL-2 homology (BH) 4 domain maintains the inactive conformation of BAK, and disrupting this domain is sufficient for constitutive BAK activation. Moreover, the entire N-terminal region preceding the BAK oligomerisation domains became disordered post-activation and remained disordered in the activated oligomer. Removal of the disordered N-terminus did not impair, but rather slightly potentiated, BAK-mediated membrane permeabilisation of liposomes and mitochondria. Together, our HDX-MS analyses reveal new insights into the dynamic nature of BAK activation on a membrane, which may provide new opportunities for therapeutic targeting.

BAK core dimers bind lipids and can be bridged by them.

BAK and BAX are essential mediators of apoptosis that oligomerize in response to death cues, thereby causing permeabilization of the mitochondrial outer membrane. Their transition from quiescent monomers to pore-forming oligomers involves a well-characterized symmetric dimer intermediate. However, no essential secondary interface that can be disrupted by mutagenesis has been identified. Here we describe crystal structures of human BAK core domain (α2-α5) dimers that reveal preferred binding sites for membrane lipids and detergents. The phospholipid headgroup and one acyl chain (sn2) associate with one core dimer while the other acyl chain (sn1) associates with a neighboring core dimer, suggesting a mechanism by which lipids contribute to the oligomerization of BAK. Our data support a model in which, unlike for other pore-forming proteins whose monomers assemble into oligomers primarily through protein-protein interfaces, the membrane itself plays a role in BAK and BAX oligomerization.

Use of Facebook to Serve Information Needs of Persons with Diabetes in the Philippines amid the COVID-19 Pandemic.

OBJECTIVES: The use of Facebook (FB) to share and gather information on diabetes is commonplace but no data is available on its use among Filipinos during the COVID-19 pandemic. We sought to determine the engagement from instructional slide decks on diabetes and its management shown on two Philippine-based FB pages under the Enhanced Community Quarantine (ECQ). METHODOLOGY: We used Insights data from the slide decks and slide shows shown on the Philippine Society of Endocrinology, Diabetes and Metabolism's (PSEDM) public FB page and the Endocrine Witch's FB page. The slide set contained a mix of mostly images and text on COVID-19 and Diabetes, dietary advice, medications and self-care in the setting of the ECQ where access to insulin, ambulatory clinics and healthy food is limited. Data was summarized in terms of post clicks, reactions, shares and comments. Total engagement rate was computed. RESULTS: We noted a high engagement rate (4-15%) in both public FB pages with higher engagement rates in slides shown in the Filipino language for most topics. The slides that gathered more shares and reactions were primarily those containing general information on COVID-19 and diabetes, nutrition including the safety of canned goods, as well as sick day rules. CONCLUSION: In the setting of the ECQ, the use of image and text-based slide-decks on the PSEDM and Endocrine Witch FB pages to communicate health information yielded high engagement.

A Randomized Controlled Trial on the Effectiveness of Short Message Service (SMS) Reminders in Improving Postpartum Follow-up among Gestational Diabetes Mellitus Patients.

OBJECTIVE: This study assessed whether short message service (SMS) reminders would improve follow-up rate among gestational diabetes mellitus (GDM) patients by 12 weeks postpartum. METHODOLOGY: In this single-center, single-blind randomized controlled trial, we assigned 308 patients with GDM to either of 2 arms, usual care alone versus usual care with SMS reminders. In the usual care group, 154 patients received a 10-minute short lecture on GDM and a 75 g oral glucose tolerance test (OGTT) request prior to discharge. In the SMS group, 154 patients received twice a week SMS reminders at 4 weeks, 8 weeks, and 10 weeks after delivery in addition to usual care. The primary outcome was clinic visit within 6 to 12 weeks postpartum with a 75 g OGTT result. RESULTS: In our population, the overall follow-up rate was 19.8% (61/308). Follow up rates were 20.1% (31/154) for the usual care group and 19.5% (30/154) for the SMS. The addition of SMS reminders was not associated with an increase in follow-up rate at 12 weeks postpartum (adjusted RR 0.98, 95% CI 0.63-1.52; p=0.932). The use of insulin or metformin for GDM control was associated with increased follow-up (adjusted RR 1.92, 95% CI 1.20-3.07; p=0.006). CONCLUSION: SMS reminders did not improve postpartum follow-up rate among GDM patients at 12 weeks postpartum.

Parkin inhibits BAK and BAX apoptotic function by distinct mechanisms during mitophagy.

The E3 ubiquitin ligase Parkin is a key effector of the removal of damaged mitochondria by mitophagy. Parkin determines cell fate in response to mitochondrial damage, with its loss promoting early onset Parkinson's disease and potentially also cancer progression. Controlling a cell's apoptotic response is essential to co-ordinate the removal of damaged mitochondria. We report that following mitochondrial damage-induced mitophagy, Parkin directly ubiquitinates the apoptotic effector protein BAK at a conserved lysine in its hydrophobic groove, a region that is crucial for BAK activation by BH3-only proteins and its homo-dimerisation during apoptosis. Ubiquitination inhibited BAK activity by impairing its activation and the formation of lethal BAK oligomers. Parkin also suppresses BAX-mediated apoptosis, but in the absence of BAX ubiquitination suggesting an indirect mechanism. In addition, we find that BAK-dependent mitochondrial outer membrane permeabilisation during apoptosis promotes PINK1-dependent Parkin activation. Hence, we propose that Parkin directly inhibits BAK to suppress errant apoptosis, thereby allowing the effective clearance of damaged mitochondria, but also promotes clearance of apoptotic mitochondria to limit their potential pro-inflammatory effect.

VDAC2 enables BAX to mediate apoptosis and limit tumor development.

Intrinsic apoptosis is critical to prevent tumor formation and is engaged by many anti-cancer agents to eliminate tumor cells. BAX and BAK, the two essential mediators of apoptosis, are thought to be regulated through similar mechanisms and act redundantly to drive apoptotic cell death. From an unbiased genome-wide CRISPR/Cas9 screen, we identified VDAC2 (voltage-dependent anion channel 2) as important for BAX, but not BAK, to function. Genetic deletion of VDAC2 abrogated the association of BAX and BAK with mitochondrial complexes containing VDAC1, VDAC2, and VDAC3, but only inhibited BAX apoptotic function. Deleting VDAC2 phenocopied the loss of BAX in impairing both the killing of tumor cells by anti-cancer agents and the ability to suppress tumor formation. Together, our studies show that efficient BAX-mediated apoptosis depends on VDAC2, and reveal a striking difference in how BAX and BAK are functionally impacted by their interactions with VDAC2.

Glycaemic responses in Asian and non-Asian people with type 2 diabetes initiating insulin glargine 100 units/mL: A patient-level pooled analysis of 16 randomised controlled trials.

AIMS: To compare outcomes between Asian and non-Asian patients with type 2 diabetes (T2D) inadequately controlled on oral antidiabetic drugs (OADs) initiating insulin glargine 100 units (U)/mL (Gla-100) in randomised controlled clinical trials. METHODS: Post hoc analysis of patient-level data (Asian n = 235; non-Asian n = 3351) from 16 trials. RESULTS: At baseline, Asian patients were younger with lower body mass index (BMI), fasting C-peptide, and fasting plasma glucose (FPG) than non-Asian patients (all P < .001). Asian patients had a higher mean glycosylated haemoglobin (HbA1c) at Week 24 and less reduction in HbA1c from baseline (7.4% vs. 7.2%; -1.3% vs. -1.6%, respectively; P = .0001), and were less likely to achieve HbA1c <7.0% (40% vs. 47%; P = .002) than non-Asian patients. Reductions in FPG and rates of hypoglycaemia were similar between Asian and non-Asian patients. Asian patients had less weight gain than non-Asian patients (+1.3 vs. +1.9 kg, respectively, P = .013). CONCLUSIONS: In our post hoc meta-analysis, Gla-100 effectively lowers HbA1c and FPG in Asian patients with T2D uncontrolled on OADs with similar incidence of hypoglycaemia and less absolute weight gain compared with non-Asian patients. At a similar FPG reduction, fewer Asian patients achieved HbA1c target <7.0%, suggesting that prandial glucose needs to be addressed.

Challenges and unmet needs in basal insulin therapy: lessons from the Asian experience.

Basal insulin therapy can improve glycemic control in people with type 2 diabetes. However, timely initiation, optimal titration, and proper adherence to prescribed basal insulin regimens are necessary to achieve optimal glycemic control. Even so, glycemic control may remain suboptimal in a significant proportion of patients. Unique circumstances in Asia (eg, limited resources, management of diabetes primarily in nonspecialist settings, and patient populations that are predominantly less educated) coupled with the limitations of current basal insulin options (eg, risk of hypoglycemia and dosing time inflexibility) amplify the challenge of optimal basal insulin therapy in Asia. Significant progress has been made with long-acting insulin analogs (insulin glargine 100 units/mL and insulin detemir), which provide longer coverage and less risk of hypoglycemia over intermediate-acting insulin (Neutral Protamine Hagedorn insulin). Furthermore, recent clinical evidence suggests that newer long-acting insulin analogs, new insulin glargine 300 units/mL and insulin degludec, may address some of the unmet needs of current basal insulin options in terms of risk of hypoglycemia and dosing time inflexibility. Nevertheless, more can be done to overcome barriers to basal insulin therapy in Asia, through educating both patients and physicians, developing better patient support models, and improving accessibility to long-acting insulin analogs. In this study, we highlight the unique challenges associated with basal insulin therapy in Asia and, where possible, propose strategies to address the unmet needs by drawing on clinical experiences and perspectives in Asia.

Conversion of Bim-BH3 from Activator to Inhibitor of Bak through Structure-Based Design.

Certain BH3-only proteins transiently bind and activate Bak and Bax, initiating their oligomerization and the permeabilization of the mitochondrial outer membrane, a pivotal step in the mitochondrial pathway to apoptosis. Here we describe the first crystal structures of an activator BH3 peptide bound to Bak and illustrate their use in the design of BH3 derivatives capable of inhibiting human Bak on mitochondria. These BH3 derivatives compete for the activation site at the canonical groove, are the first engineered inhibitors of Bak activation, and support the role of key conformational transitions associated with Bak activation.

BAK α6 permits activation by BH3-only proteins and homooligomerization via the canonical hydrophobic groove.

BAK and BAX are the essential effectors of apoptosis because without them a cell is resistant to most apoptotic stimuli. BAK and BAX undergo conformation changes to homooligomerize then permeabilize the mitochondrial outer membrane during apoptosis. How BCL-2 homology 3 (BH3)-only proteins bind to activate BAK and BAX is unclear. We report that BH3-only proteins bind inactive full-length BAK at mitochondria and then dissociate following exposure of the BAK BH3 and BH4 domains before BAK homodimerization. Using a functional obstructive labeling approach, we show that activation of BAK involves important interactions of BH3-only proteins with both the canonical hydrophobic binding groove (α2-5) and α6 at the rear of BAK, with interaction at α6 promoting an open groove to receive a BH3-only protein. Once activated, how BAK homodimers multimerize to form the putative apoptotic pore is unknown. Obstructive labeling of BAK beyond the BH3 domain and hydrophobic groove did not inhibit multimerization and mitochondrial damage, indicating that critical protein-protein interfaces in BAK self-association are limited to the α2-5 homodimerization domain.

Acute mania after levothyroxine replacement for hypothyroid-induced heart block.

Psychiatric disturbances can manifest after levothyroxine (LT4) treatment for severe hypothyroidism. We present the case of a young Filipino man with Hashimoto's thyroiditis and high-grade heart block, who was given a full replacement LT4 dose on admission. Twenty-four hours after this dose, he developed manic symptoms, which were addressed with sedatives and neuroleptics with gradual restoration of euthymia the following day. A comprehensive workup did not reveal any findings suggestive of another aetiology for either mania or heart block. We ultimately ascribed the mania as secondary to LT4, and the heart block to hypothyroidism. Although mania is more likely to be precipitated by high starting LT4 doses, reports have shown that symptoms can still arise even at lower doses and with more gradual titration, especially in long-standing hypothyroidism.

Indicators of Accurate Health Information on the Internet on the Use of Momordica Charantia in Diabetes Mellitus.

OBJECTIVES: The increasing use of the Internet as a source of health information makes the accuracy of such information crucial. An example is the use of the widely advertised bitter melon (Momordica charantia) in treating diabetes despite its unproven efficacy. This study aims to assess the accuracy of websites containing information on bitter melon's role in diabetes, to search for the presence of the proposed quality indicators, and to determine their correlation with accuracy. METHODOLOGY: An Internet search was used to generate a list of websites. The accuracy of each website was determined by comparing its content with that of a tool that was developed from authoritative sources. The presence of the proposed quality indicators, taken from published guidelines, was then correlated with accuracy. RESULTS: Of the 158 websites identified, 10 (6.33%) were characterized as "most accurate" and 21 (13.3%) as "somewhat accurate." The identified indicators of accuracy were the HONcode logo (OR 12.1, p=0.011); the author, identified as a healthcare professional (OR=6.11, p=0.008); and a citation from a peer-reviewed medical literature (OR 2.92, p=0.029). CONCLUSION: These findings suggest that most of the Internet-based information on bitter melon's role in diabetes is inaccurate. The public can use several indicators of accurate information on the use of bitter melon in diabetes to improve health care.

Prevalence of medication errors in admitted patients at the Philippine General Hospital

@#<p style="text-align: justify;"><strong>BACKGROUND:</strong> Medication errors are preventable events that can cause or lead to inappropriate drug use. Knowing the prevalence and types of errors can help us institute corrective measures and avoid adverse drug events.<br /><strong>OBJECTIVE:</strong> This study determined the prevalence of medication errors and its specific types in the four main service wards of a tertiary government training medical center.<br /><strong>METHODS:</strong> This is a retrospective, descriptive chart review study. From the master list of admissions, systematic sampling was done to retrieve the required number of charts. Relevant pages such as order sheets, nurses' notes, therapeutic sheets were photographed. For prolonged admissions, only the first 7 days were reviewed. Each chart was evaluated by two people who then met and agreed on the errors identified.<br /><strong>RESULTS:</strong> The overall prevalence of medication errors is 97.8%. Pediatrics had the most (63.3/chart), followed by Medicine, OB-Gynecology, and Surgery (7.3/chart). The most common type of errors identified were prescribing, followed by compliance, then administration errors.<br /><strong>CONCLUSION:</strong> Medication errors are present in the four main wards in our hospital. We recommend orientation of all incoming first year residents on proper ordering and prescribing of drugs, as well as a prospective observational study to determine true prevalence of all types of medication errors.</p>

Content analysis of tweets of pregnant women with diabetes

OBJECTIVES: Describe health beliefs of pregnant women with diabetes using tweets. Describe how information on diabetes in pregnancy is shared on Twitter. METHODS: Tweets by women with diabetes were identified from Symplur Signals. "Status" tweets were mapped to the Health Belief Model. Tweets by women with preexisting diabetes and gestational diabetes (GD) were analyzed separately. Links within tweets were surveyed for the Health on the Net (HON) Foundation seal. RESULTS: Women with GD tweeted about cravings and the connection of high carbohydrate meals with big babies. Perceived barriers included food restriction, hunger, lab tests, clinic consults and blood glucose monitoring. Perceived benefits of blood glucose testing and a healthy diet were linked to healthy babies. Blood glucose monitoring, weight gain, and age of gestation were cues to action. Perceived barriers of women with preexisting diabetes were feelings of helplessness, loss of control, and anger. Nine domains (9.7%) had the HON Code seal. Women with preexisting diabetes shared blog posts. Women with GD shared links from organizations. CONCLUSION: Women with GD and preexisting diabetes had differing perceptions of susceptibility, severity, barriers, benefits, cues to action, and self-efficacy; and shared links to information differently on Twitter.