Donkey milk as a non-bovine alternative: a review of its nutri-functional properties, applications, and challenges.

Elevation in incidences of cow milk protein allergies warrants the need to investigate the suitability of non-bovine milk alternatives for human consumption. Donkey milk has emerged as a potential alternative attributed to its benefits to human health. Evidently, it is a great option for infants as it closely resembles human milk. Researchers have also investigated its suitability in producing numerous dairy products. This review discusses the various nutri-functional aspects of donkey milk, its applications and challenges in the manufacturing of infant formula, yogurt, cheese, ice cream, kefir, and fermented milk. Research updates on processing techniques (thermal and non-thermal) for donkey milk preservation are also delineated. Despite abundant nutrients and desirable functional properties, the growth of the donkey milk industry is not significant. This is due to the lower yield, scattered population, and lack of regulatory standards for both products and processing. Recommendation on research gaps and obstacles in its commercialization are also addressed.

Assessment of the diagnostic efficacy of radiological and functional evaluation of primary adrenal mass and its' surgical outcomes.

INTRODUCTION: Objective of this study was to assess the diagnostic efficacy of the most commonly used radiological evaluation in form of contrast enhanced computed tomography of abdomen with adrenal protocol, basic functional evaluation and surgical outcomes of primary adrenal masses. MATERIAL AND METHODS: We have retrospectively analysed the institutional records of 108, patients admitted from August 2017 to September 2023, who had underwent surgical intervention for their adrenal mass after thorough evaluation and stabilization. RESULTS: Flank pain was the most common symptoms in 44 (40.74%) patients. Non-functional adrenal adenoma was found in 36 (33.33%) patients. Pheochromocytoma was the most the common functional adrenal mass found in 24 (22.22%) patients. CECT abdomen had suggested features of malignancy in 16(14.81%) patients. In final histopathological report 26(24.07%) patients had pheochromocytoma and 12 (11.11%) patients had adrenocortical carcinoma. CECT abdomen had sensitivity of 75%, specificity of 95.6%. Plasma free metanephrines and normetanephrine analysis had shown sensitivity of 90%, specificity of 92.86%, aldosterone to renin ratio had sensitivity of 92%, specificity of 100%. Sensitivity and specificity of the low-dose dexamethasone suppression test and plasma dehydroepiandrosterone was 100% in our study. Eighty patients (74.07%) were operated with laparoscopic adrenalectomy, 20 (18.52%) patients with open adrenalectomy. Eight patients (7.41%) were converted from laparoscopic to open. Laparoscopic approach had significantly lesser mean operating time, lesser blood loss, lesser hospitalization and lesser post-operative complications. CONCLUSION: Radiological analysis and functional analysis has shown good sensitivity and high specificity. Laparoscopic approach has advantage of lesser operative time, lesser hospitalization and lesser post-operative complications.

Volitionally regulated breathing with prolonged expiration influences food craving and impulsivity.

Introduction Previously an intervention involving volitional slow breathing reduced trait food craving with protective effects on cardiac vagal activity (CVA). Breathing with a low inspiration-to-expiration ratio (i/e) also increases CVA. High CVA was separately associated with low unregulated eating and lesser impulsivity. Hence the present study assessed breathing with a low i/e for effects on state food craving, hunger and satiety, state impulsivity, and heart rate variability (HRV) in healthy obese persons. Methods Forty obese persons were randomized to two groups. The intervention group (mean age ± SD, 41.15 ± 12.63, M: F, 10:10) practiced metronome-regulated breathing with low i/e at 12 breaths per minute (expiration 72% of total breath duration) (bpm) and attained expiration 55.8% of total breath duration, while the active control group (mean age ± SD, 44.45 ± 11.06, M: F, 13:07) sat motionless and directed their gaze and awareness to the stationary metronome without modifying their breath consciously. The HRV was recorded before, during and after breathing intervention (or control) (standard limb lead I, acquisition at 2000 Hz, with a LF filter = 0.5 Hz and HF filter = 50 Hz. Time-domain and frequency-domain HRV parameters were obtained with Kubios software. State food craving, hunger and satiety were recorded before and after the intervention/control. Results The intervention group decreased total state food craving scores and the sub-domains (i.e., desire to eat, positive reinforcement, lack of control and hunger), increased current satisfaction with food, decreased total state impulsivity (repeated measures ANOVA, p < 0.05 in all cases), increased HF-HRV and RMSSD (linear mixed model analyses with age and gender as fixed factors; p<0.05 in all cases) during the intervention compared to the preceding baseline. The intervention group also showed an increase in positive mood and a decrease in aroused and negative mood states. Conclusion Changes in state food craving and impulsivity could be related to an increase in HRV or to changes in subjective relaxation and positive mood or to both.

Muscle strength and body composition in obese adults following nine months of yoga or nutrition advice: A comparative controlled trial.

INTRODUCTION: Muscle strength is impaired in obese persons due to low physical activity, obesity-related modifications in muscle morphology and as a consequence of calorie regulation (where applicable). Previously decreased BMI and increased hand grip strength was reported following a short duration yoga intervention in obese adults. METHODS: The present comparative controlled study was conducted on two hundred and ninety seven obese adults (BMI ≥25 Kg/M2) aged between 20 and 59 years, to determine the effects of nine months of yoga or nutrition advice on muscle strength and body composition. Participants were assessed for bilateral hand grip strength, leg and back strength, and body composition at baseline, after 3 months, 6 months and 9 months of yoga or nutrition advice. BMI-adjusted bilateral hand grip strength and leg and back strength were calculated. RESULTS: In the linear mixed model analyses, there was a significant interaction effect of Time X Groups for (i) right hand grip strength (F3,668.465 = 9.297, p < 0.001), (ii) left hand grip strength (F3,673.408 = 14.469, p < 0.001), (iii) BMI-adjusted right hand grip strength (F3,650.542 = 9.954, p < 0.001) and (iv) BMI-adjusted left hand grip strength (F3,655.518 = 13.853, p < 0.001). Bonferroni corrected post-hoc analyses (padj < 0.05; in all cases) showed a significant increase in (i) bilateral hand grip strength and (ii) BMI-adjusted right and left hand grip strength in the yoga group while a decrease in (i) bilateral hand grip strength and (ii) BMI-adjusted right and left hand grip strength in the nutrition advice group. CONCLUSION: Yoga practice appears to protect and increase upper limb muscle strength in obese adults.

Traditional Nostril Yoga Breathing Practices and Oxygen Consumption: A Randomized, Cross-over Study.

Background: Traditional yoga texts describe "cross nostril breathing," with inhalation and exhalation through different nostrils. Previous research reported no clear differences in oxygen consumption during uninostril breathing (i.e., inhalation and exhalation through the same nostril), hence not supporting right and left uninostril breathing as activating or relaxing, respectively, with no research on oxygen consumed in "cross nostril breathing." Methods: Oxygen consumed during "cross nostril breathing" was measured in healthy participants (n = 47, males, 26.3 ± 6.4 years). Five sessions (viz., right nostril inspiration yoga breathing [RNIYB], left nostril inspiration yoga breathing [LNIYB], alternate nostril yoga breathing [ANYB], breath awareness (BAW), and quiet rest (QR) were conducted on separate days in random order. Sessions were 33 min in duration with pre, during, and post states. Results: Volume of oxygen consumed (VO2) and carbon dioxide eliminated (VCO2) increased during RNIYB (9.60% in VO2 and 23.52% in VCO2), LNIYB (9.42% in VO2 and 21.20% in VCO2) and ANYB (10.25% in VO2 and 22.72% in VCO2) with no significant change in BAW and QR. Diastolic blood pressure decreased during BAW and QR and after all five sessions (P < 0.05; in all cases). All comparisons were with the respective preceding state. Conclusion: During the three yoga breathing practices, the volume of oxygen consumed increased irrespective of the nostril breathed through, possibly associated with (i) conscious regulation of the breath; (ii) attention directed to the breath, and (iii) "respiration-locked cortical activation." Restriction of the study to males reduces the generalizability of the findings.

Cerebral Hemodynamics and Vagally Mediated HRV Associated with High- and Low-frequency Yoga Breathing: An Exploratory, Randomized, Crossover Study.

Background: Volitionally modifying respiration leads to changes in middle cerebral arterial (MCA) blood flow. The effect of changes in breath rate on MCA blood flow has not been reported. Aims and Objectives: To determine the effect of slow (bumblebee yoga breathing) and fast (high frequency yoga breathing) yoga breathing techniques on MCA blood flow and vagally mediated heart rate variability. Materials and Methods: Thirty participants (mean age ± standard deviation, 27.3 ± 4.2 years) were assessed on 2 separate days practicing either high frequency yoga breathing (HFYB, breath frequency 54.2/min) or slow frequency bumblebee yoga breathing (BBYB, breath frequency 3.8/min) in random order to determine the effects of changes in breath frequency on MCA hemodynamics. Assessments included transcranial Doppler sonography, vagally mediated heart rate variability (VmHRV), and respiration. Results: Both HFYB and BBYB (i) reduced MCA flow velocities, i.e., peak systolic, end diastolic, and mean flow velocities, and (ii) increased MCA pulsatility indices. There was an increase in VmHRV during BBYB based on increased power in high frequency (HF) and low frequency (LF). LF reflects VmHRV for slow breath frequencies. In BBYB the average breath rate was 3.8 breaths/min. In contrast, VmHRV decreased during HFYB (based on reduced HF power; repeated measures analysis of variance, P < 0.05, all cases). Conclusion: Hence, irrespective of the differences in breath frequency, both HFYB and BBYB appear to reduce MCA flow velocities and increase the resistance to blood flow bilaterally, although the VmHRV changed in opposite directions. MCA velocity and pulsatility changes are speculated to be associated with low global neural activity during yoga breathing.

On the origin of epitaxial rhombohedral-B4C growth by CVD on 4H-SiC.

Rhombohedral boron carbide, often referred to as r-B4C, is a potential material for applications in optoelectronic and thermoelectric devices. From fundamental thin film growth and characterization, we investigate the film-substrate interface between the r-B4C films grown on 4H-SiC (0001̄) (C-face) and 4H-SiC (0001) (Si-face) during chemical vapor deposition (CVD) to find the origin for epitaxial growth solely observed on the C-face. We used high-resolution (scanning) transmission electron microscopy and electron energy loss spectroscopy to show that there is no surface roughness or additional carbon-based interlayer formation for either substrate. Based on Raman spectroscopy analysis, we also argue that carbon accumulation on the surface hinders the growth of continued epitaxial r-B4C in CVD.

Securing patient data in the healthcare industry: A blockchain-driven protocol with advanced encryption.

BACKGROUND: Ensuring the security and privacy of patient data is a critical concern in the healthcare industry. The growing utilization of electronic data transmission and storage in medical records has amplified apprehensions about data security. However, due to varying stakeholder interests, not all data can be freely shared, necessitating the development of secure protocols. MATERIALS AND METHODS: This study presents a highly secure protocol that integrates blockchain technology, patient biometric information, and robust cryptographic algorithms (elliptic curve cryptography (ECC) and advanced encryption algorithm (AEC)) to facilitate data encryption and decryption. The protocol encompasses secure login, secure key sharing, and data sharing mechanisms among miners, offering comprehensive security measures. To validate the effectiveness of the proposed protocol, both informal and formal security analyses are conducted. The security protocol description language in Scyther is utilized to evaluate the protocol's resilience against attacks. RESULTS: The culmination of this research is a secure protocol that leverages blockchain technology and ECC for the secure storage and sharing of medical records. The protocol covers all stages, including system setup, user registration, login mechanisms, key exchange between users and blockchain, communication between blockchains, and interaction with other miners, with a steadfast emphasis on security. Furthermore, the protocol's communication and computation costs are assessed, with a comparison to existing blockchain-based schemes. Informal proofs establish the protocol's security against common attacks faced by medical institutions. Formal simulation of the protocol using the Scyther tool provides definitive evidence of its resistance to attacks. CONCLUSIONS: As a result, this protocol presents a viable real-time implementation solution for safeguarding patient data within the healthcare domain, representing a significant contribution to data security.

Long term outcomes and impact on renal function following radical cystectomy.

INTRODUCTION: To assess clinical, oncological outcomes and impact on renal function in patients who underwent the radical cystectomy with pelvic lymphadenectomy for muscle invasive and high risk non-muscle invasive transitional cell carcinoma of urinary bladder without evidence of non-regional lymph nodes and distant metastasis. MATERIALS AND METHODS: With curative intent total 156 patients underwent radical cystectomy with pelvic lymphadenectomy from January 2015 to December 2022. Total 132/156 patients had primary transitional cell carcinoma of bladder. Thirty patients, presented with obstructive nephropathy, operated after stabilization of renal function. Pre-operatively and post-operatively eGFR calculated using modified diet in renal disease formula. RESULTS: In present study 114 (86.36%) patients had high grade TCC, 70 (53.02%) patients had organ confined disease. Nodal extension seen in 74 (56.06%) patients. Perioperative mortality noted in 36 (27.2%) patients. The overall survival and recurrence free survival (RFS) over 5 years was 66.67 and 45.45%. RFS was significantly related to pathological stage, nodal status, histological-grade, positivity of surgical margin and time of surgery from diagnosis. Total 92/132 (69.7%) patients had recurrence. Pelvic recurrence in 10/92 (10.87%) whereas 82/92 (89.13%) patients had distant recurrence. Pre-operatively mean creatinine was 2.6 mg/dl and mean eGFR was 38.9 ml/h in patients who presented with obstructive nephropathy after stabilization of renal function. Post-operatively in 46/132 (34.8%) patients had improvement in eGFR while 86/132 (65.2%) patients had deterioration of eGFR over 62 months of median follow up. CONCLUSION: Radical cystectomy provides good overall survival outcomes. Pre-operative eGFR has significant impact on post-operative renal function in long term.

Precision-controlled ultrafast electron microscope platforms. A case study: Multiple-order coherent phonon dynamics in 1T-TaSe2 probed at 50 fs-10 fm scales.

We report on the first detailed beam tests attesting the fundamental principle behind the development of high-current-efficiency ultrafast electron microscope systems where a radio frequency (RF) cavity is incorporated as a condenser lens in the beam delivery system. To allow for the experiment to be carried out with a sufficient resolution to probe the performance at the emittance floor, a new cascade loop RF controller system is developed to reduce the RF noise floor. Temporal resolution at 50 fs in full-width-at-half-maximum and detection sensitivity better than 1% are demonstrated on exfoliated 1T-TaSe2 system under a moderate repetition rate. To benchmark the performance, multi-terahertz edge-mode coherent phonon excitation is employed as the standard candle. The high temporal resolution and the significant visibility to very low dynamical contrast in diffraction signals via high-precision phase-space manipulation give strong support to the working principle for the new high-brightness femtosecond electron microscope systems.

Automated Lane Centering: An Off-the-Shelf Computer Vision Product vs. Infrastructure-Based Chip-Enabled Raised Pavement Markers.

Safe autonomous vehicle (AV) operations depend on an accurate perception of the driving environment, which necessitates the use of a variety of sensors. Computational algorithms must then process all of this sensor data, which typically results in a high on-vehicle computational load. For example, existing lane markings are designed for human drivers, can fade over time, and can be contradictory in construction zones, which require specialized sensing and computational processing in an AV. But, this standard process can be avoided if the lane information is simply transmitted directly to the AV. High definition maps and road side units (RSUs) can be used for direct data transmission to the AV, but can be prohibitively expensive to establish and maintain. Additionally, to ensure robust and safe AV operations, more redundancy is beneficial. A cost-effective and passive solution is essential to address this need effectively. In this research, we propose a new infrastructure information source (IIS), chip-enabled raised pavement markers (CERPMs), which provide environmental data to the AV while also decreasing the AV compute load and the associated increase in vehicle energy use. CERPMs are installed in place of traditional ubiquitous raised pavement markers along road lane lines to transmit geospatial information along with the speed limit using long range wide area network (LoRaWAN) protocol directly to nearby vehicles. This information is then compared to the Mobileye commercial off-the-shelf traditional system that uses computer vision processing of lane markings. Our perception subsystem processes the raw data from both CEPRMs and Mobileye to generate a viable path required for a lane centering (LC) application. To evaluate the detection performance of both systems, we consider three test routes with varying conditions. Our results show that the Mobileye system failed to detect lane markings when the road curvature exceeded ±0.016 m-1. For the steep curvature test scenario, it could only detect lane markings on both sides of the road for just 6.7% of the given test route. On the other hand, the CERPMs transmit the programmed geospatial information to the perception subsystem on the vehicle to generate a reference trajectory required for vehicle control. The CERPMs successfully generated the reference trajectory for vehicle control in all test scenarios. Moreover, the CERPMs can be detected up to 340 m from the vehicle's position. Our overall conclusion is that CERPM technology is viable and that it has the potential to address the operational robustness and energy efficiency concerns plaguing the current generation of AVs.

Survivin inhibition ameliorates liver fibrosis by inducing hepatic stellate cell senescence and depleting hepatic macrophage population.

Persistent activation of hepatic stellate cells (HSCs) in the injured liver leads to the progression of liver injury from fibrosis to detrimental cirrhosis. In a previous study, we have shown that survivin protein is upregulated during the early activation of HSCs, which triggers the onset of liver fibrosis. However, the therapeutic potential of targeting survivin in a fully established fibrotic liver needs to be investigated. In this study, we chemically induced hepatic fibrosis in mice using carbon tetrachloride (CCl4) for 6 weeks, which was followed by treatment with a survivin suppressant (YM155). We also evaluated survivin expression in fibrotic human liver tissues, primary HSCs, and HSC cell line by histological analysis. αSMA+ HSCs in human and mice fibrotic liver tissues showed enhanced survivin expression, whereas the hepatocytes and quiescent (qHSCs) displayed minimal expression. Alternatively, activated M2 macrophage subtype induced survivin expression in HSCs through the TGF-ß-TGF-ß receptor-I/II signaling. Inhibition of survivin in HSCs promoted cell cycle arrest and senescence, which eventually suppressed their activation. In vivo, YM155 treatment increased the expression of cell senescence makers in HSCs around fibrotic septa such as p53, p21, and ß-galactosidase. YM155 treatment in vivo also reduced the hepatic macrophage population and inflammatory cytokine expression in the liver. In conclusion, downregulation of survivin in the fibrotic liver decreases HSC activation by inducing cellular senescence and modulating macrophage cytokine expression that collectively ameliorates liver fibrosis.

AMPK stimulation inhibits YAP/TAZ signaling to ameliorate hepatic fibrosis.

Hepatic fibrosis is driven by the activation of hepatic stellate cells (HSCs). The Hippo pathway and its effectors, YAP and TAZ, are key regulators of HSC activation and fibrosis. However, there is a lack of mechanistic understanding of YAP/TAZ regulation in HSCs. Here we show that AMPK activation leads to YAP/TAZ inhibition and HSC inactivation in vitro, while the expression of a kinase-inactive mutant reversed these effects compared to wild type AMPKɑ1. Notably, the depletion of LATS1/2, an upstream kinase of YAP/TAZ signaling, rescues YAP/TAZ activation, suggesting that AMPK may be mediating YAP/TAZ inhibition via LATS1/2. In the carbon tetrachloride mouse model of fibrosis, pharmacologic activation of AMPK in HSCs inhibits YAP/TAZ signaling and reduces fibrosis. The findings implicate AMPK as a critical regulator of YAP/TAZ signaling and HSC inactivation and highlight AMPK activation as a therapeutic target for the treatment of hepatic fibrosis.

First-in-Class Dual EZH2-HSP90 Inhibitor Eliciting Striking Antiglioblastoma Activity In Vitro and In Vivo.

Structural analysis of tazemetostat, an FDA-approved EZH2 inhibitor, led us to pinpoint a suitable site for appendage with a pharmacophoric fragment of second-generation HSP90 inhibitors. Resultantly, a magnificent dual EZH2/HSP90 inhibitor was pinpointed that exerted striking cell growth inhibitory efficacy against TMZ-resistant Glioblastoma (GBM) cell lines. Exhaustive explorations of chemical probe 7 led to several revelations such as (i) compound 7 increased apoptosis/necrosis-related gene expression, whereas decreased M phase/kinetochore/spindle-related gene expression as well as CENPs protein expression in Pt3R cells; (ii) dual inhibitor 7 induced cell cycle arrest at the M phase; (iii) compound 7 suppressed reactive oxygen species (ROS) catabolism pathway, causing the death of TMZ-resistant GBM cells; and (iv) compound 7 elicited substantial in vivo anti-GBM efficacy in experimental mice xenografted with TMZ-resistant Pt3R cells. Collectively, the study results confirm the potential of dual EZH2-HSP90 inhibitor 7 as a tractable anti-GBM agent.

Patients' Choices for Yoga Therapy: An Exploratory Cross-Sectional, Convenience-Sampling Survey from India.

In conventional healthcare, patients' preferences for their treatment are determined, though this practice has not been reported for yoga therapy. The present convenience sampling exploratory survey attempted to determine whether those seeking yoga therapy would report preferences for the way yoga therapy is implemented, the therapist's knowledge, and related aspects of yoga therapy. Responses from 426 people attending a yoga therapy institution in India were analyzed. Based on the chi-square test (p < 0.05) and Cramer's V (> 0.10), most people wished to receive yoga therapy in a group of others with a similar disease (42.25%), in a yoga institution (83.57%), and as in-person sessions (48.83%). Patients preferred yoga therapists to know about the principles of yoga (40.38%), to be well-informed generally (61.97%), and to be able to give suggestions for emotional well-being. For the majority of participants (59.4%), the reason for selecting yoga therapy was "a belief in yoga as therapy" (rather than as an add-on therapy or as a last resort). Patients' expectations of yoga therapy were positive, namely a cure of disease (79.34%) and improvement after 1 year (95.8%). Most patients (91.6%) wanted their conventional medicine practitioner to know that they were receiving yoga therapy. Although limited by the study design, survey design, and participant details available, overall results suggest that patients (1) reported specific preferences (for the implementation of yoga therapy and for yoga therapists' knowledge), (2) had expectations of yoga therapy, and (3) most often were interested in their conventional care physicians being informed about the yoga therapy they received.

Enhancing Medical Diagnosis with AI: A Focus on Respiratory Disease Detection.

Background: Artificial intelligence (AI) is revolutionizing medical diagnosis and healthcare, providing constant support to medical practitioners. Intelligent systems alleviate workload pressure while optimizing practitioner performance. AI and deep learning have also improved medical imaging and audio analysis. Material and Methods: This research focuses on predicting respiratory diseases using audio recordings from an electronic stethoscope. A convolutional neural network (CNN) was trained on a Respiratory Sound Database, augmented to generate 1,428 audio files. Techniques such as pitch shifting, time stretching, noise addition, time and frequency masking, dynamic range compression, and resampling were employed to increase the diversity and size of the training data. Result: Features were extracted from mono audio files, creating a four layer CNN with 90% accuracy. The software, developed using the CNN model and Streamlit python library, offers a new tool for early and accurate diagnosis, reducing the burden on medical practitioners and enhanci ng their performance. The study highlights AI's potential in respiratory disease detection through audio analysis. Conclusion: The software, developed using the CNN model and Streamlit python library, offers a new tool for early and accurate diagnosis, reducing the burden on medical practitioners and enhancing their performance.

Flavone-based dual PARP-Tubulin inhibitor manifesting efficacy against endometrial cancer.

Structural tailoring of the flavone framework (position 7) via organopalladium-catalyzed C-C bond formation was attempted in this study. The impact of substituents with varied electronic effects (phenyl ring, position 2 of the benzopyran scaffold) on the antitumor properties was also assessed. Resultantly, the efforts yielded a furyl arm bearing benzopyran possessing a 4-fluoro phenyl ring (position 2) (14) that manifested a magnificent antitumor profile against the Ishikawa cell lines mediated through dual inhibition of PARP and tubulin [(IC50 (PARP1) = 74 nM, IC50 (PARP2) = 109 nM) and tubulin (IC50 = 1.4 µM)]. Further investigations confirmed the ability of 14 to induce apoptosis as well as autophagy and cause cell cycle arrest at the G2/M phase. Overall, the outcome of the study culminated in a tractable dual PARP-tubulin inhibitor endowed with an impressive activity profile against endometrial cancer.

N-Heterocycle based Degraders (PROTACs) Manifesting Anticancer Efficacy: Recent Advances.

Proteolysis Targeting Chimeras (PROTACs) technology has emerged as a promising strategy for the treatment of undruggable therapeutic targets. Researchers have invested a great effort in developing druggable PROTACs; however, the problems associated with PROTACs, including poor solubility, metabolic stability, cell permeability, and pharmacokinetic profile, restrict their clinical utility. Thus, there is a pressing need to expand the size of the armory of PROTACs which will escalate the chances of pinpointing new PROTACs with optimum pharmacokinetic and pharmacodynamics properties. N- heterocycle is a class of organic frameworks that have been widely explored to construct new and novel PROTACs. This review provides an overview of recent efforts of medicinal chemists to develop N-heterocycle-based PROTACs as effective cancer therapeutics. Specifically, the recent endeavors centred on the discovery of PROTACs have been delved into various classes based on the E3 ligase they target (MDM2, IAP, CRBN, and other E3 ligases). Mechanistic insights revealed during the biological assessment of recently furnished Nheterocyclic- based PROTACs constructed via the utilization of ligands for various E3 ligases have been discussed.

Addressing the challenges of AI-based telemedicine: Best practices and lessons learned.

Telemedicine is the use of technology to provide healthcare services and information remotely, without requiring physical proximity between patients and healthcare providers. The coronavirus disease 2019 (COVID-19) pandemic has accelerated the rapid growth of telemedicine worldwide. Integrating artificial intelligence (AI) into telemedicine has the potential to enhance and expand its capabilities in addressing various healthcare needs, such as patient monitoring, healthcare information technology (IT), intelligent diagnosis, and assistance. Despite the potential benefits, implementing AI in telemedicine presents challenges that can be overcome with physician-guided implementation. AI can assist physicians in decision-making, improve healthcare delivery, and automate administrative tasks. To ensure optimal effectiveness, AI-powered telemedicine should comply with existing clinical practices and adhere to a framework adaptable to various technologies. It should also consider technical and scientific factors, including trustworthiness, reproducibility, usability, availability, and cost. Education and training are crucial for the appropriate use of new healthcare technologies such as AI-enabled telemedicine. This article examines the benefits and limitations of AI-based telemedicine in various medical domains and underscores the importance of physician-guided implementation, compliance with existing clinical practices, and appropriate education and training for healthcare providers.

Cellular stress in the pathogenesis of nonalcoholic steatohepatitis and liver fibrosis.

The burden of chronic liver disease is rising substantially worldwide. Fibrosis, characterized by excessive deposition of extracellular matrix proteins, is the common pathway leading to cirrhosis, and limited treatment options are available. There is increasing evidence suggesting the role of cellular stress responses contributing to fibrogenesis. This Review provides an overview of studies that analyse the role of cellular stress in different cell types involved in fibrogenesis, including hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells and macrophages.