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Abstract The PIM kinase family, consisting of PIM1, PIM2, and PIM3, is a group of serine/threonine protein kinases crucial for cellular growth, immunoregulation, and oncogenesis. PIM1 kinase is often overexpressed in solid and hematopoietic malignancies, promoting cell survival, proliferation, migration, and senescence by activating key genes. In vitro and in vivo studies have established the oncogenic potential of PIM1 kinases. These kinases have been implicated in tumor progression, metastasis, and resistance to chemotherapy, underscoring their potential as a therapeutic target for cancer therapy. This review delves into the intricate molecular mechanisms through which PIM1 interacts with specific substrates in different tumor tissues, leading to diverse outcomes in various human cancers. Over the past decade, the inhibition of PIM1 in cancers has garnered significant attention as a potential standalone treatment. Various in vitro, in vivo, and early clinical trial data have provided support for this approach to varying extents. Novel compounds that inhibit PIM1 kinase have shown effectiveness and a favorable toxicity profile in preclinical studies. Several of these substances are now being studied in clinical trials due to their promising outcomes. This article provides a thorough examination of the PIM1 kinase pathways and the recent advancements in producing PIM1 kinase inhibitors for the treatment of cancer.

Abstract Conditional regulation is a highly beneficial system for studying the function of essential genes in Plasmodium falciparum and dimerizable Cre recombinase (DiCre) is a recently adapted conditional regulation system suitable for this purpose. In the DiCre system, two inactive fragments of Cre are reconstituted to form a functionally active enzyme in the presence of rapamycin. Different loci have been targeted to generate parasite lines that express the DiCre enzyme. Here, we have used marker-free CRISPR-Cas9 gene editing to integrate the DiCre cassette in a redundant cg6 locus. We have shown the utility of the newly generated ∆cg6DC4 parasites in mediating robust, rapid, and highly specific excision of exogenously encoded gfp sequence. The ∆cg6DC4 parasites are also capable of conditional excision of an endogenous parasite gene, PF3D7_1246000. Conditional deletion of PF3D7_1246000 did not cause any inhibition in the asexual proliferation of the parasites. Furthermore, the health and morphology of the mutant parasites were comparable to that of the control parasites in Giemsa smears. The availability of another stable DiCre parasite strain competent for conditional excision of target genes will expedite functional characterization and validation of novel drug and vaccine targets against malaria.

Abstract Third-party punishment (TPP) is an altruistic behavior or sense willing to punish transgressors as a third party not directly involved in the transgression. TPP is observed worldwide, regardless of tradition and culture, and is essential for morality in human society. Moreover, even preverbal infants display TPP-like judgement, suggesting that TPP is evolutionarily conserved and innate. Thus, it is possible that non-human animals display TPP-like behavior, although TPP has been said to be human-specific. We investigated whether or not male mature Wistar rats displayed TPP-like behaviors when they witnessed deadly aggression by an unknown aggressive mouse toward another unknown victim mouse. Normally reared rats did not display TPP-like behaviors, but rats reared with extensive affectionate handling by human caretakers as beloved pets contacted the unknown aggressive mice in a gentle manner leading to reduced aggression toward the unknown victim mice, even when the aggressive mice fought back. Furthermore, the handled rats touched unknown rat pups that were drowning in water and anesthesia-induced comatose rats more frequently than control rats. These findings suggest a possibility that TPP is not in fact human-specific and innate but rather an acquired behavior that flourishes in affectionate circumstances.

Background: Pancytopenia is a common hematological entity and a striking feature of many life-threatening illnesses. Aims and Objectives: The study was conducted to identify the etiology of pancytopenia. (i) To find out primary bone marrow (BM) causes of pancytopenia. (ii) To evaluate the spectrum of BM morphology in pancytopenia cases. Materials and Methods: This hospital-based observational study was conducted between June 2021 and May 2022 in a tertiary care hospital in Dibrugarh in all pancytopenia cases of age above 12 years and meeting the inclusion criteria. After taking written consent, detailed history, clinical examination, and baseline investigations were done followed by BM examination. Results: Mean age was 45.39±15.49 years. Majority were males 41 (56.9%) and 31 (43.1%) were females. The most common cause of pancytopenia was Megaloblastic anemia (30.5%) cases, followed by aplastic anemia (18%) and myelodysplastic syndromes (16.7%). About 72 (100%) had pallor followed by weakness (86.1%), bleeding tendencies (70.8%), and fever (52.8%). Conclusion: The study underscores the critical role of BM biopsy in the diagnostic workup of pancytopenia. It confirms that BM biopsy is indispensable for identifying the diverse etiologies of pancytopenia and in implementing the appropriate therapy.

Arthroscopic shoulder surgeries are routinely practiced in many orthopedic centers for diagnostic and therapeutic purposes. The patient is commonly made to lie in a lateral position to carry out the procedure. We had a 71-year-old patient who underwent right shoulder arthroscopy for rotator cuff injury; the duration of surgery was 300 min. The patient developed subcutaneous edema over the neck and anterior chest. Further evaluation revealed airway edema as well. The patient was shifted to ICU for monitoring and overnight ventilation. Other radiological investigations confirmed the edema in subcutaneous and deep tissues of the neck and chest. The patient was extubated the next day morning after the edema improved. She was shifted to the ward for further management. Airway edema after shoulder arthroscopy, though uncommon, can be predicted in susceptible patients with prolonged surgeries and excess fluid irrigation. Timely diagnosis and intervention with coordination among the treating teams can result in positive outcomes.

Abstract Background Betulinic acid (BA) has been well investigated for its antiproliferative and mitochondrial pathway-mediated apoptosis-inducing effects on various cancers. However, its poor solubility and off-target activity have limited its utility in clinical trials. Additionally, the immune modulatory role of betulinic acid analogue in the tumor microenvironment (TME) is largely unknown. Here, we designed a potential nanotherapy for colorectal cancer (CRC) with a lead betulinic acid analogue, named as 2c, carrying a 1,2,3-triazole-moiety attached to BA through a linker, found more effective than BA for inhibiting CRC cell lines, and was chosen here for this investigation. Epithelial cell adhesion molecule (EpCAM) is highly overexpressed on the CRC cell membrane. A single-stranded short oligonucleotide sequence, aptamer (Apt), that folds into a 3D-defined architecture can be used as a targeting ligand for its specific binding to a target protein. EpCAM targeting aptamer was designed for site-specific homing of aptamer-conjugated-2c-loaded nanoparticles (Apt-2cNP) at the CRC tumor site to enhance therapeutic potential and reduce off-target toxicity in normal cells. We investigated the in vitro and in vivo therapeutic efficacy and anti-tumorigenic immune response of aptamer conjugated nanotherapy in CRC-TME. Methods After the characterization of nanoengineered aptamer conjugated betulinic acid nanotherapy, we evaluated therapeutic efficacy, tumor targeting efficiency, and anti-tumorigenic immune response using cell-based assays and mouse and rat models. Results We found that Apt-2cNP improved drug bioavailability, enhanced its biological half-life, improved antiproliferative activity, and minimized off-target cytotoxicity. Importantly, in an in vivo TME, Apt-2cNP showed promising signs of anti-tumorigenic immune response (increased mDC/pDC ratio, enhanced M1 macrophage population, and CD8 T-cells). Furthermore, in vivo upregulation of pro-apoptotic while downregulation of anti-apoptotic genes and significant healing efficacy on cancer tissue histopathology suggest that Apt-2cNP had predominantly greater therapeutic potential than the non-aptamer-conjugated nanoparticles and free drug. Moreover, we observed greater tumor accumulation of the radiolabeled Apt-2cNP by live imaging in the CRC rat model. Conclusions Enhanced therapeutic efficacy and robust anti-tumorigenic immune response of Apt-2cNP in the CRC-TME are promising indicators of its potential as a prospective therapeutic agent for managing CRC. However, further studies are warranted. Graphical abstract

Abstract Impedance-matched Marx generators (IMGs) are considered next generation pulsed-power drivers because of their long lifetime (> 10,000 shots), repetition rate (> 0.1-Hz), fast rise time (~ 100-ns), and high-energy-delivery efficiency (~ 90%). “TITAN” is a 14-stage IMG designed to deliver 1-TW to a 2-Ω matched load. In this paper, design, simulation, and experimental results for six stages of TITAN including its triggering system, air delivery system, and pulse shaping are presented. To achieve efficiency over 85% and maximize the capability of an IMG, synchronized triggering, reduced pre-fire rate, and pulse shaping ability are crucial. In this paper, novel engineering solutions are introduced, tested, and proven to overcome those challenges. 6-stage TITAN, powered by 102 identical bricks and 102 field-distortion-triggered gas switches, could generate ~ 600-kA and ~ 700-kV across a ~ 0.9-Ω matched load when fully charged to ± 100-kV. In these experiments, 6-stage TITAN is tested up to ± 70-kV charge voltage which delivers a peak power of 330-GW to a 1.2-Ω resistive load.

Introduction Fat grafts have been in used since 1962 for small central perforations, with a success rate ranging from 86 to 100%. Platelet-rich plasma (PRP) containing platelet concentrations greater than 1 million platelets/μL assist the healing process by various means. Current data suggests improved healing when tympanoplasty is performed using temporalis fascia grafts if PRP is added during surgery.

Summary: Background: Deployment and access to state-of-the-art precision medicine technologies remains a fundamental challenge in providing equitable global cancer care in low-resource settings. The expansion of digital pathology in recent years and its potential interface with diagnostic artificial intelligence algorithms provides an opportunity to democratize access to personalized medicine. Current digital pathology workstations, however, cost thousands to hundreds of thousands of dollars. As cancer incidence rises in many low- and middle-income countries, the validation and implementation of low-cost automated diagnostic tools will be crucial to helping healthcare providers manage the growing burden of cancer. Methods: Here we describe a low-cost ($230) workstation for digital slide capture and computational analysis composed of open-source components. We analyze the predictive performance of deep learning models when they are used to evaluate pathology images captured using this open-source workstation versus images captured using common, significantly more expensive hardware. Validation studies assessed model performance on three distinct datasets and predictive models: head and neck squamous cell carcinoma (HPV positive versus HPV negative), lung cancer (adenocarcinoma versus squamous cell carcinoma), and breast cancer (invasive ductal carcinoma versus invasive lobular carcinoma). Findings: When compared to traditional pathology image capture methods, low-cost digital slide capture and analysis with the open-source workstation, including the low-cost microscope device, was associated with model performance of comparable accuracy for breast, lung, and HNSCC classification. At the patient level of analysis, AUROC was 0.84 for HNSCC HPV status prediction, 1.0 for lung cancer subtype prediction, and 0.80 for breast cancer classification. Interpretation: Our ability to maintain model performance despite decreased image quality and low-power computational hardware demonstrates that it is feasible to massively reduce costs associated with deploying deep learning models for digital pathology applications. Improving access to cutting-edge diagnostic tools may provide an avenue for reducing disparities in cancer care between high- and low-income regions. Funding: Funding for this project including personnel support was provided via grants from NIH/NCI R25-CA240134, NIH/NCI U01-CA243075, NIH/NIDCR R56-DE030958, NIH/NCI R01-CA276652, NIH/NCI K08-CA283261, NIH/NCI-SOAR 25CA240134, SU2C (Stand Up to Cancer) Fanconi Anemia Research Fund – Farrah Fawcett Foundation Head and Neck Cancer Research Team Grant, and the European Union Horizon Program (I3LUNG).

Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

Synovitis is a disorder that develops when the synovial tissue or joint lining becomes inflamed. The term pigmented villonodular synovitis (PVNS) refers to a form of tenosynovial giant cell neoplasm affecting the tendon and joint soft-tissue lining. We describe the rare case of a 37-year-old male presenting with complaints of swelling in the left knee following trauma. Patients have a limited range of motion. There is a previous history of an accident 1 year back for which he was operated. Recent magnetic resonance imaging (MRI) revealed anterior cruciate ligament and posterior cruciate ligament avulsion fracture. The clinical diagnosis and radiologic findings were in favor of PVNS. Histopathological examination revealed the presence of fungus. It was further confirmed by fungal culture, for which the patient was given antifungals and was further followed up in the orthopedics outpatient clinic. Thus, we diagnosed fungal synovitis in a patient who came with clinical presentation and MRI findings suggestive of PVNS.

Objective: To determine the association between vaccination status and mortality among critically ill patients admitted in a dedicated Covid hospital of Tripura who required invasive mechanical ventilation. Material and Methods: This study was conducted at a dedicated Covid hospital of Tripura for a period of six months, i.e., from June 2021 to November 2021. A total of 304 patients were enrolled for this study. Baseline epidemiological, radiological data along with other information like heart rate, pulse rate, oxygen saturation (SpO2), etc., were collected through patient record sheet in all cases during hospitalization. Statistical analysis was done by using SPSS 25 version. Results: Admission and mortality rates in hospital and advanced oxygen support like bi-level positive airway pressure (BiPAP), high-flow nasal cannula (HFNOC), and ventilator use incidences were higher in non-vaccinated patients (17.1%) in comparison to double-dose-vaccinated (0.98%) and single-dose (2.3%)-vaccinated patients. Conclusion: This retrospective data analysis of Covid-19 positive patients admitted in the dedicated Covid Hospital of Tripura suggests that severe infection, need for invasive and non-invasive ventilation, and death were significantly less in the vaccinated patients as compared to the vaccine-naive one.

Abstract Coronary artery disease (CAD) imposes a significant economic burden in developing countries like India. Timely diagnosis and treatment should be prioritized to mitigate the disease. Current diagnostic tools being invasive and less specific raise the need to develop less invasive and more reliable molecular biomarkers. MicroRNAs (miRNAs) are an emerging class of molecules that can serve as a potential source of non-invasive biomarkers for CAD. The objective of this study was to determine the potential of circulatory miRNAs as diagnostic biomarkers in CAD. In this study, we have reported two microRNAs, miR-128-3p and miR-195-5p in the serum of CAD patients in Indian Population. A total of 124 subjects were recruited which included 89 angiographically proven CAD patients and 35 control subjects. Our results show a significant decrease in the levels of miR-128-3p in CAD patients while there were no significant changes in the levels of miR-195-5p. Further bioinformatics analysis revealed the potential role of miR-128-3p in cholesterol homeostasis. Altered homeostasis due to cholesterol accumulation in macrophages is the driving force behind formation of foam cells which in turn accelerates the progression of CAD. Here, we have shown that miR-128-3p increases cholesterol levels in macrophages by decreasing cholesterol efflux in-vitro.

Introduction: Laparoscopic surgeries currently represent the mainstay of surgical modalities. Pneumoperitoneum imposes significant intraoperative haemodynamic alterations, which are more pronounced in elderly patients and those with co-morbid conditions. Inadequate pain relief in the perioperative period may result in various physiological and psychological traumas. Aim: To investigate the effects of magnesium sulphate, dexmedetomidine, and lignocaine on the haemodynamic responses and postoperative analgesia in patients undergoing laparoscopic abdominal surgeries. Materials and Methods: This double-blinded, randomised clinical study was conducted in the general surgery operation theatre, Post-anaesthetic Care Unit (PACU), and the male and female surgery ward of RG Kar Medical College and Hospital, Kolkata, West Bengal, India from March 1, 2021, to March 1, 2022. The study involved 105 subjects assigned to Group-L, who received an injection of lignocaine as a loading dose of 1.5 mg/kg intravenously over 2-4 minutes before induction, followed by a continuous infusion of 2 mg/kg/hour throughout the surgery. Group-M received a loading dose of MgSO4 at 30 mg/kg over 15 minutes before induction, followed by 15 mg/kg/hour throughout the surgery, and Group-D received a loading dose of dexmedetomidine at 1 mcg/kg over 10 minutes before induction, followed by a continuous infusion of 0.5 mcg/kg/min throughout the surgery. Data on Heart Rate (HR), Mean Arterial Pressure (MAP), and the total dose of rescue analgesic administered in the postoperative 24 hours were recorded and analysed using Analysis of Variance (ANOVA) and Tukey’s Honestly Significant Difference (HSD) test, as well as the Chi-square test where applicable. A p-value of less than 0.05 was considered statistically significant. Results: The groups were comparable in terms of demographic variables and baseline haemodynamic status. The average age in Group-D was 39.13±9.48 years, in Group-M was 37.30±8.14 years, and in Group-L was 36.5±7.2 years (p=0.26). Group-D had 60% males, Group-M had 57% males, and Group-L had 60% males. The mean Body Mass Index (BMI) of Group-D was 25.9±2.03 (kg/m2), Group-L (Lignocaine) was 24.7±2.7, and Group-M (Magnesium Sulphate) was 23.8±3.2. Dexmedetomidine was found to be superior in maintaining haemodynamic stability throughout the perioperative period (Preinduction HR: Group-D=79.43, Group-L=79.06, Group-M=82.09; Postinduction HR: Group-D=86.49, Group-M=65.91, Group-L=72.69). There was a significant decrease in postintubation MAP, most pronounced in the Magnesium Sulphate and Dexmedetomidine groups. Post-pneumoperitoneum, the surge in MAP was most effectively prevented by Dexmedetomidine. The lowest amount of rescue analgesic (injection Diclofenac in mg) was used in the Dexmedetomidine group (55.86±5.05), followed by the Lignocaine group (126.43±17.69). Patients in the Magnesium group required the highest amount of rescue analgesic (156.43±7.91). The number of patients receiving rescue analgesia was significantly higher in the Lignocaine and Magnesium Sulphate groups (Group-D: 6.5±3.14565, Group-L: 14.75±7.36, Group-M: 18.25±8.057). Conclusion: Dexmedetomidine was more effective in maintaining haemodynamic stability throughout the perioperative period and exhibited superior postoperative analgesic properties. Magnesium Sulphate and lignocaine were more effective in preventing postintubation surges.

Abstract Polyploidy is typically described as the condition wherein a cell or organism has more than two complete sets of chromosomes. Occurrence of polyploidy is a naturally occurring phenomenon in the body’s development and differentiation processes under normal physiological conditions. However, in pathological conditions, the occurrence of polyploidy is documented in numerous disorders, including cancer, aging and diabetes. Due to the frequent association that the polyploidy has with these pathologies and physiological process, understanding the cause and consequences of polyploidy would be beneficial to develop potential therapeutic applications. Many of the genetic and epigenetic alterations leading to cancer, diabetes and aging are linked to signaling pathways. Nonetheless, the specific signaling pathway associated with the cause and consequences of polyploidy still remains largely unknown. Mammalian/mechanistic target of rapamycin (mTOR) plays a key role in the coordination between eukaryotic cell growth and metabolism, thereby simultaneously respond to various environmental inputs including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in the regulation of many fundamental cellular processes that range from protein synthesis to autophagy. Dysregulated mTOR signaling has been found to be implicated in various disease progressions. Importantly, there is a strong correlation between the hallmarks of polyploidy and dysregulated mTOR signaling. In this review, we explore and discuss the molecular connection between mTOR signaling and polyploidy along with its association with cancer, diabetes and aging. Additionally, we address some unanswered questions and provide recommendations to further advance our understanding of the intricate relationship between mTOR signaling and polyploidy.

Abstract The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

Background: Transfusion of blood and blood products is a double-edged sword, so it should be used judiciously. The primary aim of the centralized hemovigilance program is to improve transfusion safety. Aims and Objectives: To determine the frequency, distribution, and types of transfusion reactions (TRs) occurring in patients, reported to the blood center in a tertiary care hospital in North East India. Materials and Methods: A retrospective study was conducted in State of The Art Model Blood Center, Assam Medical College and Hospital for 1 year from July 2022 to June 2023. Data were collected from TR records as per the hemovigilance reporting format and analyzed. Results: During the study, 38,165 blood products were issued. 41 (0.11%) TRs were recorded, out of which 25 (61%) occurred with packed red cell transfusion followed by whole blood transfusion (39%). The most common type was febrile non-hemolytic TR (51.2%) followed by allergic reactions (39%). Conclusion: The frequency of adverse TRs was low (0.11%), which may be due to the management of a few cases by the treating clinician itself. Most reactions occurred with packed red blood cells (PRBC) transfusion, the most common type being febrile non-hemolytic TR, which may be due to the presence of leukocytes, inflammatory mediators in leftover plasma during PRBC preparation, which can be standardized by the use of leukoreduced blood products. Hemovigilance will help to strengthen the quality and safety of blood transfusion.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has presented a challenge to maintaining good physical and mental health worldwide. Aim: The aim of this study was to find the relationship between mental health status and well-being among Northeast Indian people during the outbreak of the COVID-19 pandemic. Materials and Methods: The present study was an online cross-sectional survey carried out among the people of the Northeast India population. The questionnaire was converted into Google Forms and distributed via E-mail, WhatsApp, Messenger application, LinkedIn, and other social media platforms in contact with the investigators. Results: A total number of 565 responses were obtained including both male (n = 243) and female (n = 322) participants. In the study, mild stress was found in 30.1% of the participants, 5.3% had moderate stress, 1.2% had severe stress and 4.0% had extremely severe stress. Mild anxiety was found in 13.1%, 21.8% had a moderate level of anxiety, 5.7% had severe anxiety, and a least 3.5% had an extremely severe level of anxiety. Mild depression was reported by 17.7%, 16.3% had moderate depression, 3.5% had severe depression, and 2.7% had extremely severe depression. Person correlation shows that well-being has a significant negative correlation with stress (r = −0.482; P < 0.01), anxiety (r = −0.323; P < 0.01), and depression (r = −513; P < 0.01). The finding of the study shows that well-being has a significant negative correlation with stress, anxiety, and depression. Conclusion: The study concludes that the COVID-19 pandemic has had a profound impact on mental and physical health, and mental health responses need to be treated with psychosocial interventions to prevent mental health crises in the general population during a pandemic.

BackgroundLarge-scale crisis events such as COVID-19 often have secondary impacts on individuals’ mental well-being. University students are particularly vulnerable to such impacts. Traditional survey-based methods to identify those in need of support do not scale over large populations and they do not provide timely insights. We pursue an alternative approach through social media data and machine learning. Our models aim to complement surveys and provide early, precise, and objective predictions of students disrupted by COVID-19. ObjectiveThis study aims to demonstrate the feasibility of language on private social media as an indicator of crisis-induced disruption to mental well-being. MethodsWe modeled 4124 Facebook posts provided by 43 undergraduate students, spanning over 2 years. We extracted temporal trends in the psycholinguistic attributes of their posts and comments. These trends were used as features to predict how COVID-19 disrupted their mental well-being. ResultsThe social media–enabled model had an F1-score of 0.79, which was a 39% improvement over a model trained on the self-reported mental state of the participant. The features we used showed promise in predicting other mental states such as anxiety, depression, social, isolation, and suicidal behavior (F1-scores varied between 0.85 and 0.93). We also found that selecting the windows of time 7 months after the COVID-19–induced lockdown presented better results, therefore, paving the way for data minimization. ConclusionsWe predicted COVID-19–induced disruptions to mental well-being by developing a machine learning model that leveraged language on private social media. The language in these posts described psycholinguistic trends in students’ online behavior. These longitudinal trends helped predict mental well-being disruption better than models trained on correlated mental health questionnaires. Our work inspires further research into the potential applications of early, precise, and automatic warnings for individuals concerned about their mental health in times of crisis.

Tailgut cyst, or retrorectal cystic hamartoma, is a rare congenital malformation originating from retrorectal or presacral space. It stands as an embryonic vestige of the hindgut's postnatal component. Owing to its rarity, undiagnosed asymptomatic cases and diverse array of clinical presentations that potentially mimic other diseases, correct diagnosis is often delayed. It can present at any age but is most prevalent in middle-aged females, often remaining asymptomatic and eluding detection during digital rectal examinations. Postoperative histopathological examination is the definitive diagnostic method. This case report highlights an unusual presentation of a tailgut cyst as an underlying etiology for lower back pain in a 17-year-old female patient, emphasizing the importance of considering it as a potential differential diagnosis for intractable lower back pain, especially in young females. Timely recognition of this condition is pivotal for precise management and better patient outcomes.

Background: Supraglottic airway devices are frequently used instead of endotracheal intubation in laparoscopic surgeries. Two such devices, I-gel (IG) and Baska mask (BM), have been compared with respect to their sealing properties and leak fraction (LF) in comparison to the endotracheal tube. Aims and Objectives: The aim of the present study is to compare the performance of IG and BM with endotracheal tube in patients undergoing laparoscopic cholecystectomy under general anesthesia. Materials and Methods: In this randomized trial, 84 patients scheduled for laparoscopic cholecystectomy under general anesthesia were randomized to group (endotracheal tube [ETT], n=28), group BM (BM, n=28), or group IG (IG, n=28). All the patients received standard general anesthesia and the airway was maintained with either of three devices. The primary outcomes were the difference in the LF and airway sealing pressure (ASP) at different time points before and after pneumoperitoneum. Secondary outcomes were insertion-time, number of insertion attempts, and gastric insufflations. Heart rate and blood pressure were recorded. Complications such as sore throat, coughing, laryngospasm, blood staining of the device, and aspiration were noted. Results: P-values of LF of the three groups at time points T- after insertion (Ti), T-after pneumoperitoneum (Tp), and T- after peritoneal deflation (Tr) were 0.000 each and P-values of ASP at those time points were 0.000 each, respectively. Insertion time was significantly less for IG than ET (P

Background: A common emergency of the abdomen with a significant morbidity and fatality rate is gastrointestinal perforation. In the treatment of perforation, surgery is important. Scoring systems are required for prognosis, comparing, and auditing surgical procedures. Methods: A prospective study conducted at a single center with a sample of 100 individuals who had hollow viscus perforation was carried out. Investigations or a laparotomy were used to confirm the diagnosis. The death rate, anastomotic leak, dehiscence, infection, and respiratory issues, as well as hospital and intensive care unit stays were all followed prospectively over a 30-day period for all patients. Results: Duodenal perforation was the commonest among hollow viscus perforations. The 20–40 age range was the most severely affected. Males suffer more than females. Complications can be avoided with a correct early diagnosis and suitable treatment. The site, size, age, and number of perforations all affect the surgical method. P-POSSUM and APACHE II scores were strongly correlated with outcomes such as post-operative wound dehiscence, respiratory issues, ICU stay, and hospital stay. When predicting mortality, POSSUM score was found to be superior to MPI. Conclusions: Gastrointestinal perforations result in substantial morbidity and occasionally fatality. The most frequent reason for an acute abdomen requiring prompt, effective surgical intervention is hollow viscus perforation. Complications can be avoided with an accurate early diagnosis and sufficient treatment. The surgical strategy is determined by the perforation's location, size, age, and quantity.

Abstract Contrary to popular belief, agriculture is becoming more data-driven with artificial intelligence and Internet-of-Things (IoT) playing crucial roles. In this paper, the integrated processing executed by various sensors combined as an IoT pack and driving an intelligent agriculture management system designed for rainfall prediction and fruit health monitoring have been included. The proposed system based on an AI aided model makes use of a Convolutional Neural Network (CNN) with long short-term memory (LSTM) layer for rainfall prediction and a CNN with SoftMax layer along with a few deep learning pre-trained models for fruit health monitoring. Another model that works as a combined rainfall predictor and fruit health recognizer is designed using a CNN + LSTM and a multi-head self-attention mechanism which proves to be effective. The entire system is cloud resident and available for use through an application.

Background: Acute respiratory distress syndrome caused by severe acute respiratory syndrome coronavirus 2, is a challenge to health-care system in the recent times. The nonavailability of specific treatment and rapid spread through aerosols has impacted the countries worldwide. Research on the subject is continuous, to understand the pathology and pathophysiology of the condition. In this regard, diagnosis of the disease, severity stratification and clinical prognostication helps the clinician to plan the management. Literature is silent on clinical biomarkers for this novel disease. Hence, a study was carried out to find out a suitable clinical biomarker for the disease. Methodology: The author carried out a retrospective analysis of the fatal case records of a tertiary center COVID intensive care unit to evaluate whether Carbon dioxide gradient can be used as an end-stage marker of COVID pneumonia. A record-based observational study was conducted and data were collected from the fatal case documents after an institutional ethical committee clearance. Results: A total of 42 fatal cases were analyzed. Carbon dioxide retention was found in more than 90% of cases and raised carbon dioxide gradient (>5 mmHg) was found in more than 50% of cases. The average days of mechanical ventilation was 9 days and on average, after 5 days of ventilation patients developed raised carbon dioxide gradient. Conclusion: We conclude that raised carbon dioxide gradient may be chosen as an end-stage marker for COVID pneumonia though large group studies are recommended.

Abstract Background Oral mucositis remains a significant complication during cancer therapy with no effective treatment. Gold nanoparticles offer anti-inflammatory, antioxidant properties with low toxicity. This study systematically reviews the literature assessing gold nanoparticles in the management of oral mucositis in animal models. Methods A literature search was undertaken using MEDLINE, Embase, PubMed, and Web of Science databases, using the format for Systematic Review Centre for Laboratory Animal Experimentation. Prior to the review, the protocol was registered in the systematic review register, PROSPERO (registration no. CRD42021272169). Outcome measures included ulceration, histopathological scores, inflammatory mediators, microbial growth, and pain. Study quality was analysed by SYRCLE risk-of-bias tool. Results Only one study met the inclusion criteria, documenting reduction in ulceration, inflammatory, and oxidative biomarkers. Exposure to AuNPs prevented inflammatory response induced by 5-fluorouracil in oral mucosa of hamsters. However, a high risk of bias necessitates further research. Conclusion This review identifies a potential therapeutic strategy for prevention and management of oral mucositis. It also provides future direction for gold nanoparticle research in oral mucositis; however, there is lack of sufficient evidence to derive any conclusion. Research with standardized parameters including nanoparticle size, capping agent, surface charge, and appropriate oral mucositis animal models will establish risk–benefit balance and margin of safety for therapeutic use of gold nanoparticles for oral mucositis.

Abstract Saprolegnia parasitica is responsible for devastating infections in fish and poses a tremendous threat to the global aquaculture industry. Presently, no safe and effective control measures are available, on the contrary, use of banned toxic compounds against the pathogen is affecting humans via biomagnification routes. This pioneering study aims to design an effective multi-epitope multi-target vaccine candidate against S. parasitica by targeting key proteins involved in the infection process. The proteins were analyzed and linear B-cell epitopes, MHC class I, and class II epitopes were predicted. Subsequently, highly antigenic epitopes were selected and fused to a highly immunogenic adjuvant, 50S ribosomal protein L7/L12, to design a multi-epitope chimeric vaccine construct. The structure of the vaccine was generated and validated for its stereochemical quality, physicochemical properties, antigenicity, allergenicity, and virulence traits. Molecular docking analyses demonstrated strong binding interactions between the vaccine and piscine immune receptors (TLR5, MHC I, MHC II). Molecular dynamics simulations and binding energy calculations of the complexes, further, reflected the stability and favorable interactions of the vaccine and predicted its cytosolic stability. Immune simulations predicted robust and consistent kinetics of the immune response elicited by the vaccine. The study posits the vaccine as a promising solution to combat saprolegniasis in the aquaculture industry.

Abstract Esophageal carcinoma (ESCA) is a leading cause of cancer-related death worldwide, and certain oral and intestinal pathogens have been associated with cancer development and progression. We asked if esophageal microbiomes had shared alterations that could provide novel biomarkers for ESCA risk. We extracted DNA from tumor and non-tumor tissue of 212 patients in the NCI-MD case control study and sequenced the 16S rRNA gene (V3-4), with TCGA ESCA RNA-seq (n = 172) and WGS (n = 123) non-human reads used as validation. We identified four taxa, Campylobacter, Prevotella, Streptococcus, and Fusobacterium as highly enriched in esophageal cancer across all cohorts. Using SparCC, we discovered that Fusobacterium and Prevotella were also co-enriched across all cohorts. We then analyzed immune cell infiltration to determine if these dysbiotic taxa were associated with immune signatures. Using xCell to obtain predicted immune infiltrates, we identified a depletion of megakaryocyte-erythroid progenitor (MEP) cells in tumors with presence of any of the four taxa, along with enrichment of platelets in tumors with Campylobactor or Fusobacterium. Taken together, our results suggest that intratumoral presence of these co-occurring bacterial genera may confer tumor promoting immune alterations that allow disease progression in esophageal cancer.

Introduction: There is rising concern about vitamin D deficiency around the globe due to its increasing association with multiple medical disorders. Diabetes Mellitus (DM) is an established risk factor for atherosclerotic disorders, and Carotid Artery IntimaMedia Thickness (CIMT) is considered a radiological marker of subclinical atherosclerosis. Aim: To find a correlation between serum 25-hydroxy vitamin D (25-(OH)-D) levels and CIMT among patients with DM. Materials and Methods: A hospital-based cross-sectional study was conducted, including 100 adult patients with Type 2 DM who were admitted to the Department of Medicine at SCB Medical College and Hospital in Cuttack, Odisha, India from October 2020 to September 2021. Vitamin D deficiency was defined as serum 25-(OH)-D levels

Introduction: Laparoscopic cholecystectomy is now preferred over the open procedure due to advantages such as reduced blood loss and shorter hospital stays. However, concerns have been raised regarding the potential for increased Intra-abdominal Pressure (IAP) during laparoscopic procedures, which may impact haemodynamic stability and respiratory parameters. However, there is a lack of comprehensive analysis directly comparing both surgical approaches from both haemodynamic and capnographic perspectives. Aim: To compare the haemodynamic and capnographic changes between laparoscopic and open cholecystectomy. Materials and Methods: This randomised clinical study was conducted at Department of Anaesthesiology, Assam Medical College and Hospital, Dibrugarh, Assam, India from May 2021 to June 2022. The study included 300 patients scheduled for cholecystectomy, divided into two groups: Laparoscopic Cholecystectomy (LC) Group I (n=150) and Open Cholecystectomy (OC) Group II (n=150). Haemodynamic parameters, including Pulse Rate (PR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP), and Oxygen Saturation (SpO2 ), were recorded. Capnographic parameters, such as End-Tidal Carbon Dioxide (EtCO2 ) levels, were also measured at regular intervals. Data analysis was performed using the student’s t-test and Chi-square test with Statistical Package for Social Sciences (SPSS) version 21.0 software and Microsoft excel. Results: There were no significant differences in age, body weight, and sex distribution between Group I and Group II. However, significant differences were observed in PR and SBP at 15 minutes (PR: 101.46 and 95.86; SBP: 148.57 and 140.97), 30 minutes (PR: 104.52 and 99.82; SBP: 141.28 and 136.07), and 45 minutes (PR: 102.52 and 97.70; SBP: 140.59 and 133.95) (p-value

Abstract Energy storage devices (ESD) which are intended to power electronic devices, used in close contact of human skin, are desirable to be safe and non-toxic. In light of this requirement, Zn based energy storage devices seem to provide a viable pathway as they mostly employ aqueous based electrolytes which are safe and non-toxic in their functioning. Additionally, having a flexible ESD will play a crucial role as it will enable the ESD to conform to the varying shapes and sizes of wearable electronics which they energize. In this work, we have developed an inkjet-printed Zinc ion battery (IPZIB) with planar electrode configuration over bond paper substrate. Zn has been used as the negative electrode, MnO2 is used as the positive electrode with Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) as the active binder. Conducting tracks of reduced graphene oxide (rGO) are used to construct the current collector on the paper substrate. The fabricated IPZIB delivered a high discharge capacity of 300.14 mAh g−1 at a current density of 200 mA g−1. The energy density of the IPZIB is observed as 330.15 Wh kg−1 at a power density of 220 W kg−1 and retains an energy density of 94.36 Wh kg−1 at a high power density of 1650 W kg−1. Finally, we have demonstrated the capability of the IPZIB to power a LED at various bending and folding conditions which indicates its potential to be used in the next generation flexible and wearable electronic devices.

Abstract The growing popularity of nano-fertilization around the world for enhancing yield and nutrient use efficiency has been realized, however its influence on soil microbial structure is not fully understood. The purpose of carrying out this study was to assess the combined effect of nano and conventional fertilizers on the soil biological indicators and crop yield in a wheat–maize system. The results indicate that the at par grain yield of wheat and maize was obtained with application of 75% of recommended nitrogen (N) with full dose of phosphorus (P) and potassium (K) through conventional fertilizers along with nano-N (nano-urea) or nano-N plus nano-Zn sprays and N100PK i.e. business as usual (recommended dose of fertilizer). Important soil microbial property like microbial biomass carbon was found statistically similar with nano fertilizer-based management (N75PK + nano-N, and N75PK + nano-N + nano-Zn) and conventional management (N100PK), during both wheat and maize seasons. The experimental data indicated that the application of foliar spray of nano-fertilizers along with 75% N as basal is a sustainable nutrient management approach with respect to growth, yield and rhizosphere biological activity. Furthermore, two foliar sprays of nano-N or nano-N + nano-Zn curtailed N requirement by 25%, furthermore enhanced soil microbial diversity and the microbial community structure. The specific microbial groups, including Actinobacteria, Bacteroidia, and Proteobacteria, were present in abundance and were positively correlated with wheat and maize yield and soil microbial biomass carbon. Thus, one of the best nutrient management approaches for sustaining productivity and maintaining sound microbial diversity in wheat–maize rotation is the combined use of nano-fertilizers and conventional fertilizers.

The onset of malaria causes the induction of various inflammatory markers in the host’s body, which in turn affect the body’s homeostasis and create several cerebral complications. Polarization of myeloid-derived suppressor cells (MDSCs) from the classically activated M1 to alternatively activated M2 phenotype increases the secretion of pro-inflammatory molecules. Treatment with recombinant IL-33 (rIL-33) not only alters this MDSC’s polarization but also targets the glycolysis pathway of the metabolism in MDSCs, rendering them less immunosuppressive. Along with that, the Helper T-cells subset 17 (Th17)/T regulatory cells (Tregs) ratio is skewed towards Th17, which increases inflammation by producing more IL-17. However, treating with rIL-33 also helps to restore this ratio, which brings back homeostasis. During malaria infection, there is an upregulation of IL-12 production from dendritic cells along with a distorted myeloid dendritic cells (mDC)/plasmacytoid dendritic cells (pDC) ratio towards mDCs promoting inflammation. Administering rIL-33 will also subvert this IL-12 production and increase the population of pDC in the host’s immune system during malaria infection, thus restoring mDC/pDC to homeostasis. Therefore, treatment with rIL-33 to reduce the pro-inflammatory signatures and maintenance of immune homeostasis along with the increase in survivability could be a potential therapeutic approach for cerebral malaria.

Eukaryotic chromatin is organized into functional domains, that are characterized by distinct proteomic compositions and specific nuclear positions. In contrast to cellular organelles surrounded by lipid membranes, the composition of distinct chromatin domains is rather ill described and highly dynamic. To gain molecular insight into these domains and explore their composition, we developed an antibody-based proximity biotinylation method targeting the RNA and proteins constituents. The method that we termed antibody-mediated proximity labelling coupled to mass spectrometry (AMPL-MS) does not require the expression of fusion proteins and therefore constitutes a versatile and very sensitive method to characterize the composition of chromatin domains based on specific signature proteins or histone modifications. To demonstrate the utility of our approach we used AMPL-MS to characterize the molecular features of the chromocenter as well as the chromosome territory containing the hyperactive X chromosome in Drosophila. This analysis identified a number of known RNA-binding proteins in proximity of the hyperactive X and the centromere, supporting the accuracy of our method. In addition, it enabled us to characterize the role of RNA in the formation of these nuclear bodies. Furthermore, our method identified a new set of RNA molecules associated with the Drosophila centromere. Characterization of these novel molecules suggested the formation of R-loops in centromeres, which we validated using a novel probe for R-loops in Drosophila. Taken together, AMPL-MS improves the selectivity and specificity of proximity ligation allowing for novel discoveries of weak protein–RNA interactions in biologically diverse domains.

BackgroundSubstance misuse presents significant global public health challenges. Understanding transitions between substance types and the timing of shifts to polysubstance use is vital to developing effective prevention and recovery strategies. The gateway hypothesis suggests that high-risk substance use is preceded by lower-risk substance use. However, the source of this correlation is hotly contested. While some claim that low-risk substance use causes subsequent, riskier substance use, most people using low-risk substances also do not escalate to higher-risk substances. Social media data hold the potential to shed light on the factors contributing to substance use transitions. ObjectiveBy leveraging social media data, our study aimed to gain a better understanding of substance use pathways. By identifying and analyzing the transitions of individuals between different risk levels of substance use, our goal was to find specific linguistic cues in individuals’ social media posts that could indicate escalating or de-escalating patterns in substance use. MethodsWe conducted a large-scale analysis using data from Reddit, collected between 2015 and 2019, consisting of over 2.29 million posts and approximately 29.37 million comments by around 1.4 million users from subreddits. These data, derived from substance use subreddits, facilitated the creation of a risk transition data set reflecting the substance use behaviors of over 1.4 million users. We deployed deep learning and machine learning techniques to predict the escalation or de-escalation transitions in risk levels, based on initial transition phases documented in posts and comments. We conducted a linguistic analysis to analyze the language patterns associated with transitions in substance use, emphasizing the role of n-gram features in predicting future risk trajectories. ResultsOur results showed promise in predicting the escalation or de-escalation transition in risk levels, based on the historical data of Reddit users created on initial transition phases among drug-related subreddits, with an accuracy of 78.48% and an F1-score of 79.20%. We highlighted the vital predictive features, such as specific substance names and tools indicative of future risk escalations. Our linguistic analysis showed that terms linked with harm reduction strategies were instrumental in signaling de-escalation, whereas descriptors of frequent substance use were characteristic of escalating transitions. ConclusionsThis study sheds light on the complexities surrounding the gateway hypothesis of substance use through an examination of web-based behavior on Reddit. While certain findings validate the hypothesis, indicating a progression from lower-risk substances such as marijuana to higher-risk ones, a significant number of individuals did not show this transition. The research underscores the potential of using machine learning with social media analysis to predict substance use transitions. Our results point toward future directions for leveraging social media data in substance use research, underlining the importance of continued exploration before suggesting direct implications for interventions.

We analyzed the risk factors and outcomes of antenatally diagnosed congenital diaphragmatic hernia (CDH) from a tertiary-care children’s hospital following in-utero transfer. A total of 41 antenatally detected cases of CDH were included; 30 were live-born and 11 were still-born. The primary outcome was postnatal survival. The secondary outcome was the probable factor affecting survival. No medical termination of the pregnancy was done. The mean gestational age at diagnosis was 23 weeks. The diagnostic accuracy of antenatal ultrasonography was 40/41 (97.5%). Lung-to-head ratio (LHR) was 1 in 10 cases (survived 8), and LHR was not recorded in 11 cases (survived 4). Overall survival was 14/41 (34.1%). Survival in fetuses with polyhydramnios was 0% (n=3; survived 0), associated anomalies were 33.3% (n=3; survived 1), and liver herniation was 22.2% (n=9; survived 2). Postnatally, significant risk factors included a low Apgar score, the need for ventilation, and neonatal intensive care unit (NICU) management. Survival in live-born cases was 14/30 (46.6%) and in operated cases was 14/19 (73.6%). We concluded that antenatal ultrasound had a high accuracy rate for detecting CDH. Antenatal risk factors affecting outcomes were low LHR, maternal polyhydramnios, liver herniation, and associated malformations. Postnatal risk factors included a low Apgar score, NICU admission, and a need for ventilation. The overall survival rate, as well as the survival rates for live-borns and those undergoing surgery, were 34.1%, 46.6%, and 73.6%, respectively. This data will guide clinicians in counseling the families of antenatally diagnosed CDH.

Objectives This study aimed to examine the distribution of daily salt intake across the hypertension care cascade and assess the proportional distribution of these care cascade categories across various salt consumption level.Design A population-based national cross-sectional study.Settings Data from the Bangladesh STEPS 2018 survey were used, encompassing both urban and rural strata within all eight divisions. National estimates were generated from weighted data.Participants A diverse population of 6754 men and women aged 18–69 years was included in the study.Outcome measures Daily salt consumption was estimated using the spot urine sodium concentration following Tanaka equation. Distribution of salt intake among different categories of hypertension care cascade, including hypertensives, aware of hypertension status, on treatment and under control, was assessed.Results Individuals with hypertension consume more salt on average (9.18 g/day, 95% CI 9.02 to 9.33) than those without hypertension (8.95 g/day, 95% CI 8.84 to 9.05) (p

Abstract BackgroundLeprosy leads to nerve damage and slow-healing ulcers, which are treatable with routine therapy. There has been a recent resurgence of interest in the use of honey for the treatment of different kinds of wounds. ObjectiveThe aim of this study, Honey Experiment on Leprosy Ulcer (HELP), is to evaluate the healing properties of raw, unadulterated African honey in comparison with normal saline dressing for the treatment leprosy ulcers. MethodsThis is a multicenter, comparative, prospective, single-blinded, parallel-group, and 1:1 individually randomized controlled trial to be conducted at The Leprosy Referral Hospital, Chanchaga in Minna, Niger State, North Central Nigeria, and St. Benedict Tuberculosis and Leprosy Rehabilitation Hospital in Ogoja, Cross River State, South-South Nigeria. Raw, unadulterated honey will be used in the ulcer dressing of eligible, consenting participants in the intervention group, whereas those in the control group will be treated by dressing with normal saline. The main outcomes will be the proportion of complete healing and the rate of healing up to 84 days after randomization. Follow-up will be conducted 6 months after randomization. We aim to enroll 90‐130 participants into the study. Blinded observers will examine photographs of ulcers to determine the outcomes. ResultsThe recruitment of trial participants began on March 14, 2022, and has been continuing for approximately 24 months. ConclusionsOur study will provide an unbiased estimate of the effect of honey on the healing of neuropathic ulcers.

Background: Microvascular damage is one of the most important etiopathogenetic and clinical characteristics of systemic sclerosis (SSc). Nailfold capillaroscopy (NFC) is a simple, non-invasive, and inexpensive imaging technique to assess the skin microcirculation. The aim of this study was to determine the association between NFC findings and clinical features in patients with SSc. Methods: This study was done in the Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from July 2019 to August 2020. Twenty-nine adult patients with SSc were selected according to ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) criteria 2013. NFC variables (capillary loss, avascular area, giant capillary, microhemorrhage and neoangiogenesis) and their NFC patterns (nonspecific, early, active, and late scleroderma) were analyzed using a dynamic nailfold capillaroscope. Their associations with disease duration, skin thickness score, interstitial lung disease (ILD), pulmonary hypertension (PH) and peripheral vascular involvement (pitting scar, and others) were examined. Results: Among 29 patients, scleroderma patterns were present in 27 (93.1%) patients. Thirteen (44.8%) patients had late scleroderma pattern. Early scleroderma pattern and active scleroderma patterns were observed in 7 (24.1%) patients. Disease duration was significantly associated with avascular area (P=0.04) and NFC pattern (P=0.001). Microhemorrhage was significantly associated (P=0.04) with PH, but NFC pattern was associated with ILD (P=0.03). Conclusion: NFC pattern found to be significantly associated with disease duration and ILD. Among the individual NFC findings, avascular area shows association with disease duration and microhaemorrhage showed association with pulmonary hypertension in SSc patients.

Summary: Background: BC2001 showed combining chemotherapy (5-FU + mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. Methods: RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). Primary endpoint: invasive loco-regional control (ILRC); secondary overall survival. Findings: Hypoxia affected overall survival (HR = 1.30; 95% CI 0.99–1.70; p = 0.062): more uncertainty for ILRC (HR = 1.29; 95% CI 0.82–2.03; p = 0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n = 90, HR 1.69; 95% CI 0.99–2.89 p = 0.057) but not conventional (n = 207, HR 0.70; 95% CI 0.28–1.80, p = 0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n = 51; HR 14.2; 95% CI 1.7–119; p = 0.015) but not conventional (n = 24, HR 1.04; 95% CI 0.07–15.5, p = 0.978) radiotherapy. Interpretation: Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial. Funding: Cancer Research UK, NIHR, MRC.

Pleomorphic undifferentiated sarcoma (PUS) is an extremely aggressive soft-tissue sarcoma that occurs most commonly in the trunk and the extremities but is extremely rare in the kidney. This entity has no distinctive clinical or radiological signs for diagnosis. It has high local recurrence and distant metastasis rates along with poor prognosis. We describe a case of PUS of the left kidney with urinary bladder metastases. Radiological investigations suggested an initial diagnosis of multifocal urothelial carcinoma; however, a definitive and confirmatory diagnosis of PUS was made on the basis of histopathological and immunohistochemical examination. Subsequently, left nephroureterectomy along with bladder cuff excision was performed and postoperative histopathology revealed PUS. Follow-up investigations revealed metastatic deposits of tumor in the base of the urinary bladder for which an endoscopic surgery of transurethral resection of the bladder tumor was performed. The histopathological findings were consistent with metastatic high-grade PUS of the kidney with metastasis to the bladder.

Suicide is the second leading cause of death among individuals aged 5 to 24 in the United States (US). However, the precursors to suicide often do not surface, making suicide prevention challenging. This study aims to develop a machine learning model for predicting suicide ideation (SI), suicide planning (SP), and suicide attempts (SA) among adolescents in the US during the coronavirus pandemic. We used the 2021 Adolescent Behaviors and Experiences Survey Data. Class imbalance was addressed using the proposed data augmentation method tailored for binary variables, Modified Synthetic Minority Over-Sampling Technique. Five different ML models were trained and compared. SHapley Additive exPlanations analysis was conducted for explainability. The Logistic Regression model, identified as the most effective, showed superior performance across all targets, achieving high scores in recall: 0.82, accuracy: 0.80, and area under the Receiver Operating Characteristic curve: 0.88. Variables such as sad feelings, hopelessness, sexual behavior, and being overweight were noted as the most important predictors. Our model holds promise in helping health policymakers design effective public health interventions. By identifying vulnerable sub-groups within regions, our model can guide the implementation of tailored interventions that facilitate early identification and referral to medical treatment.

BackgroundHealth misinformation and myths about treatment for opioid use disorder (OUD) are present on social media and contribute to challenges in preventing drug overdose deaths. However, no systematic, quantitative methodology exists to identify what types of misinformation are being shared and discussed. ObjectiveWe developed a multistage analytic pipeline to assess social media posts from Twitter (subsequently rebranded as X), YouTube, Reddit, and Drugs-Forum for the presence of health misinformation about treatment for OUD. MethodsOur approach first used document embeddings to identify potential new statements of misinformation from known myths. These statements were grouped into themes using hierarchical agglomerative clustering, and public health experts then reviewed the results for misinformation. ResultsWe collected a total of 19,953,599 posts discussing opioid-related content across the aforementioned platforms. Our multistage analytic pipeline identified 7 main clusters or discussion themes. Among a high-yield data set of posts (n=303) for further public health expert review, these included discussion about potential treatments for OUD (90/303, 29.8%), the nature of addiction (68/303, 22.5%), pharmacologic properties of substances (52/303, 16.9%), injection drug use (36/303, 11.9%), pain and opioids (28/303, 9.3%), physical dependence of medications (22/303, 7.2%), and tramadol use (7/303, 2.3%). A public health expert review of the content within each cluster identified the presence of misinformation and myths beyond those used as seed myths to initialize the algorithm. ConclusionsIdentifying and addressing misinformation through appropriate communication strategies could be an increasingly important component of preventing overdose deaths. To further this goal, we developed and tested an approach to aid in the identification of myths and misinformation about OUD from large-scale social media content.

Virulent strain Pseudomonas aeruginosa isolated from Mahananda River exhibited the highest hemolytic activity and virulence factors and was pathogenic to fish as clinical signs of hemorrhagic spots, loss of scales, and fin erosions were found. S3 was cytotoxic to the human liver cell line (WRL-68) in the trypan blue dye exclusion assay. Genotype characterization using whole genome analysis showed that S3 was similar to P. aeruginosa PAO1. The draft genome sequence had an estimated length of 62,69,783 bp, a GC content of 66.3%, and contained 5916 coding sequences. Eight genes across the genome were predicted to be related to hemolysin action. Antibiotic resistance genes such as class C and class D beta-lactamases, fosA, APH, and catB were detected, along with the strong presence of multiple efflux system genes. This study shows that river water is contaminated by pathogenic P. aeruginosa harboring an array of virulence and antibiotic resistance genes which warrants periodic monitoring to prevent disease outbreaks.

Regulated cell death is a key component of the innate immune response, which provides the first line of defense against infection and homeostatic perturbations. However, cell death can also drive pathogenesis. The most well-defined cell death pathways can be categorized as nonlytic (apoptosis) and lytic (pyroptosis, necroptosis, and PANoptosis). While specific triggers are known to induce each of these cell death pathways, it is unclear whether all cell types express the cell death proteins required to activate these pathways. Here, we assessed the protein expression and compared the responses of immune and non-immune cells of human and mouse origin to canonical pyroptotic (LPS plus ATP), apoptotic (staurosporine), necroptotic (TNF-α plus z-VAD), and PANoptotic (influenza A virus infection) stimuli. When compared to fibroblasts, both mouse and human innate immune cells, macrophages, expressed higher levels of cell death proteins and activated cell death effectors more robustly, including caspase-1, gasdermins, caspase-8, and RIPKs, in response to specific stimuli. Our findings highlight the importance of considering the cell type when examining the mechanisms regulating inflammation and cell death. Improved understanding of the cell types that contain the machinery to execute different forms of cell death and their link to innate immune responses is critical to identify new strategies to target these pathways in specific cellular populations for the treatment of infectious diseases, inflammatory disorders, and cancer.