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Abstract Background Primary cutaneous follicle centre lymphoma (PCFCL) and primary cutaneous marginal zone lymphoma (PCMZL) are indolent radiosensitive lymphomas, with national guidelines recommending 24 Grey (Gy) in 12 fractions, despite shorter regimens showing no difference in overall survival. Multiple studies demonstrate 4 Gy in two fractions is effective in other indolent lymphomas. Shorter regimens may result in less toxicity for patients. Objectives We aim to characterise local control rates in PCFCL and PCMZL treated with radiation therapy (RT) with 4 Gy in two fractions. Methods From a single institution database, we retrospectively identified all patients with PCFCL and PCMZL treated with 4 Gy in two fractions between 2011 and 2022. Prior topical or systemic treatments were permitted. T‐cell or high‐grade B‐cell cutaneous lymphomas, or those with less than 6 months follow‐up, were excluded. Primary outcomes were rates of response and local failure per lesion as determined by a radiation oncologist and oncologic dermatologist. Results Forty‐three consecutive patients with 98 lesions treated were identified. Twenty‐four (56%) of the patients had PCMZL, and the remainder had PCFCL. Most lesions (97%) received RT with electrons. The complete response or partial response rate was 94%. Six local failures were identified (6%). With a median follow‐up of 2.75 years, 1‐, 2‐ and 3‐year local failure‐free survival were 94%, 94% and 92%, respectively. There was minimal acute toxicity, no late toxicity and no cosmesis issues. No clinical features were predictive of local failure. Conclusions Ultra‐low dose radiation was associated with high rates of local control and minimal toxicity and may reduce personal burden and financial toxicity in appropriately selected patients.

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is a major global health concern, particularly affecting those with weakened immune systems, including the elderly. CD4+ T cell response is crucial for immunity against M.tb, but chronic infections and aging can lead to T cell exhaustion and senescence, worsening TB disease. Mitochondrial dysfunction, prevalent in aging and chronic diseases, disrupts cellular metabolism, increases oxidative stress, and impairs T‐cell functions. This study investigates the effect of mitochondrial transplantation (mito‐transfer) on CD4+ T cell differentiation and function in aged mouse models and human CD4+ T cells from elderly individuals. Mito‐transfer in naïve CD4+ T cells is found to promote protective effector and memory T cell generation during M.tb infection in mice. Additionally, it improves elderly human T cell function by increasing mitochondrial mass and altering cytokine production, thereby reducing markers of exhaustion and senescence. These findings suggest mito‐transfer as a novel approach to enhance aged CD4+ T cell functionality, potentially benefiting immune responses in the elderly and chronic TB patients. This has broader implications for diseases where mitochondrial dysfunction contributes to T‐cell exhaustion and senescence.

ABSTRACT Background This study examines the perceptions of the Australian public canvassed in 2021 during the COVID‐19 pandemic about their health system compared to four previous surveys (2008, 2010, 2012 and 2018). Methods In 2021, a nationwide online survey was conducted with a representative sample of Australians (N = 5100) recruited via market research panels. The results were compared to previous nationwide Australian survey samples from 2018 (N = 1024), 2012 (N = 1200), 2010 (N = 1201) and 2008 (N = 1146). The survey included questions consistent with previous polls regarding self‐reported health status and overall opinions of, and confidence in, the Australian health system. Results There was an increase in the proportion of respondents reporting positive perceptions at each survey between 2008 and 2021, with a significantly higher proportion of respondents expressing a more positive view of the Australian healthcare system in 2021 compared to previous years (χ2(8, N = 9645) = 487.63, p

Abstract Gut microbiome dysbiosis is a major contributing factor to several pathological conditions. However, the mechanistic understanding of the communication between gut microbiota and extra‐intestinal organs remains largely elusive. Extracellular vesicles (EVs), secreted by almost every form of life, including bacteria, could play a critical role in this inter‐kingdom crosstalk and are the focus of present study. Here, we present a novel approach for isolating lipopolysaccharide (LPS)+ bacterial extracellular vesicles (bEVLPS) from complex biological samples, including faeces, plasma and the liver from lean and diet‐induced obese (DIO) mice. bEVLPS were extensively characterised using nanoparticle tracking analyses, immunogold labelling coupled with transmission electron microscopy, flow cytometry, super‐resolution microscopy and 16S sequencing. In liver tissues, the protein expressions of TLR4 and a few macrophage‐specific biomarkers were assessed by immunohistochemistry, and the gene expressions of inflammation‐related cytokines and their receptors (n = 89 genes) were measured using a PCR array. Faecal samples from DIO mice revealed a remarkably lower concentration of total EVs but a significantly higher percentage of LPS+ EVs. Interestingly, DIO faecal bEVLPS showed a higher abundance of Proteobacteria by 16S sequencing. Importantly, in DIO mice, a higher number of total EVs and bEVLPS consistently entered the hepatic portal vein and subsequently reached the liver, associated with increased expression of TLR4, macrophage markers (F4/80, CD86 and CD206), cytokines and receptors (Il1rn, Ccr1, Cxcl10, Il2rg and Ccr2). Furthermore, a portion of bEVLPS escaped liver and entered the peripheral circulation. In conclusion, bEV could be the key mediator orchestrating various well‐established biological effects induced by gut bacteria on distant organs.

Abstract Objective Protocols to evaluate for myocardial infarction (MI) using high‐sensitivity cardiac troponin (hs‐cTn) have the potential to drive costs upward due to the added sensitivity. We performed an economic evaluation of an accelerated protocol (AP) to evaluate for MI using hs‐cTn to identify changes in costs of treatment and length of stay compared with conventional testing. Methods We performed a planned secondary economic analysis of a large, cluster randomized trial across nine emergency departments (EDs) from July 2020 to April 2021. Patients were included if they were 18 years or older with clinical suspicion for MI. In the AP, patients could be discharged without further testing at 0 h if they had a hs‐cTnI

Abstract Background Trust and distrust have shaped health behaviour during the COVID‐19 pandemic. Since the start of the pandemic, misinformation and polarization eroded trust across the United States. In states like Michigan, pandemic restrictions led to significant unrest. Michiganders also faced disproportionate morbidity and mortality from COVID‐19 during this period. Objective The objective of this qualitative study was to understand the individual experiences of trust in low‐income Michiganders during the early COVID‐19 pandemic. Participants Twenty‐four participants at or below 200% of the federal poverty line who resided in Michigan were recruited for this study. Approach Interviews were conducted during the winter of 2020 using a formal interview guide that addressed sources of information, perceptions of risk and exposure, protective behaviours and impacts of the pandemic at home, work and in receiving healthcare. Results Thematic analysis showed that themes of trust and distrust emerged in multiple facets of our participants' experiences, including in the context of information sources, the behaviours of others, health, financial security, employment and overall safety. Trust and distrust in low‐income communities often stemmed from significant financial and economic vulnerabilities and instability in access to healthcare that was exacerbated in the pandemic. Furthermore, participant trust was shaped by internal (e.g., relationships with others) and external (e.g., source of information, social inequity) factors that influenced their perceptions and experiences during the pandemic. Conclusion Trust has played an important role in many aspects of the experiences of low‐income communities during the COVID‐19 pandemic. This is important for clinicians to consider as COVID‐19 becomes endemic, and trust continues to impact patients' approaches to vaccines, testing and treatment options. Patient or Public Contribution This study was designed and conducted with the assistance and input of the members of the DECIDERS Steering Committee, a diverse statewide network of community members in Michigan. The DECIDERS team allows community members to have a voice in the design and conduct of health research, and collaborates with researchers to improve health across the state of Michigan.

Abstract Background Chromosomal microarray (CMA) is commonly utilized in the obstetrics setting. CMA is recommended when one or more fetal structural abnormalities is identified. CMA is also commonly used to determine genetic etiologies for miscarriages, fetal demise, and confirming positive prenatal cell‐free DNA screening results. Methods In this study, we retrospectively examined 523 prenatal and 319 products‐of‐conception (POC) CMA cases tested at Nationwide Children's Hospital from 2011 to 2020. We reviewed the referral indications, the diagnostic yield, and the reported copy number variants (CNV) findings. Results. In our cohort, the diagnostic yield of clinically significant CNV findings for prenatal testing was 7.8% (n = 41/523) compared to POC testing (16.3%, n = 52/319). Abnormal ultrasound findings were the most common indication present in 81% of prenatal samples. Intrauterine fetal demise was the common indication identified in POC samples. The most common pathogenic finding observed in all samples was isolated trisomy 21, detected in seven samples. Conclusion Our CMA study supports the clinical utility of prenatal CMA for clinical management and identifying genetic etiology in POC arrays. In addition, it provides insight to the spectrum of prenatal and POC CMA results as detected in an academic hospital clinical laboratory setting that serves as a reference laboratory.

Abstract Mitochondrial dysfunction alters cellular metabolism, increases tissue oxidative stress, and may be principal to the dysregulated signaling and function of CD4+ T lymphocytes in the elderly. In this proof of principle study, it is investigated whether the transfer of functional mitochondria into CD4+ T cells that are isolated from old mice (aged CD4+ T cells), can abrogate aging‐associated mitochondrial dysfunction, and improve the aged CD4+ T cell functionality. The results show that the delivery of exogenous mitochondria to aged non‐activated CD4+ T cells led to significant mitochondrial proteome alterations highlighted by improved aerobic metabolism and decreased cellular mitoROS. Additionally, mito‐transferred aged CD4+ T cells showed improvements in activation‐induced TCR‐signaling kinetics displaying markers of activation (CD25), increased IL‐2 production, enhanced proliferation ex vivo. Importantly, immune deficient mouse models (RAG‐KO) showed that adoptive transfer of mito‐transferred naive aged CD4+ T cells, protected recipient mice from influenza A and Mycobacterium tuberculosis infections. These findings support mitochondria as targets of therapeutic intervention in aging.

Background. Nontyphoidal salmonella (NTS) are responsible for food-borne gastroenteritis and bacteremia, in immunosuppressed individuals. Antibiotic resistance in NTS is on the rise. This study reports the prevalence and antimicrobial susceptibility of nontyphoidal salmonella in clinical samples. Study Design. This is a hospital record-based cross-sectional, retrospective study. Methods. In our study, inpatient samples such as blood (n = 13546), urine (n = 11,333), pus (n = 1,010), and stool (n = 926) samples were cultured to isolate etiological agents in the microbiology department from January 2017 to June 2019. Relevant details such as duration of fever, platelet count, hemoglobin, WBC count, immune status, and mode of treatment were noted from the medical records. Data were analyzed, and continuous variables were expressed as mean and categorical variables as percentages. Results. A total of 24 NTS serovars were isolated, which included ten isolates from blood, five each from urine and pus, and four from stool samples. Of the NTS, five were Salmonella enterica subsp. enterica, three were S.enterica serovar Typhimurium, one was S.enterica subsp. diarizonae, and 15 S.enterica serovars could not be serologically differentiated. All were susceptible to ampicillin, chloramphenicol, and cefuroxime. However, 16.6% of NTS was resistant to ceftriaxone, 4% to cotrimoxazole, 58% to ciprofloxacin, and 75% to nalidixic acid. Conclusions. A low prevalence of NTS responsible for invasive infections is seen in this part of the country. Few isolates were resistant to more than one antibiotic. A higher rate of resistance to ceftriaxone is the cause of concern. Awareness of the distribution of NTS serogroups is of epidemiological and public health significance.

Excessive gingival display (EGD) is one of the most common aesthetic concerns, and its correction often presents a challenge to periodontists. It has a multifactorial etiology, and this article describes a case involving hypermobile upper lip (HUL), altered passive eruption (APE), and vertical maxillary excess (VME). Upon investigation, a positive collum angle and marked subnasal skeletal depression were observed. In this context, it is noted that during a spontaneous smile, the upper lip retracts and gets lodged in this depression. The rehabilitation plan includes included aesthetic crown lengthening via gingivectomy using Chu’s proportional gauge for altered passive eruption and filling the subnasal depression by PMMA (polymethylmethacrylate) bone cement. The entire treatment plan was digitalised using cutting edge methods such as computed tomography (CT), cone beam computed tomography (CBCT), and 3D printers for virtual planning of the defect’s position, size, and shape. No postoperative complications were reported. After six months, the patient exhibited a harmonious smile with reduced exposed gingiva.

Abstract Background Lifestyle is associated with meningioma risk in the general population. Aims We assessed longitudinal associations between lifestyle‐associated factors and subsequent meningiomas in childhood cancer survivors. Methods and results Childhood cancer survivors age ≥18 years in the St. Jude Lifetime Cohort Study were evaluated for body composition, self‐reported physical activity, cardiopulmonary fitness, muscle strength, smoking, and alcohol consumption at baseline. Time to first meningioma analyses were performed, adjusted for sex, age at diagnosis and baseline assessment, treatment decade, and childhood cancer treatment exposures. The study included 4,072 survivors (47% female; [mean (SD)] 9 (6) years at diagnosis; 30 (8.5) years at the start of follow‐up, with 7.0 (3.3) years of follow‐up). 30% of the participants were survivors of acute lymphoblastic leukemia and 29% of the participants had received cranial radiation. During follow‐up, 90 participants developed ≥1 meningioma, of whom 73% were survivors of acute lymphoblastic leukemia, with cranial radiation being the strongest risk factor (relative risk [RR] 29.7, 95% confidence interval [CI] 10.6‐83.2). Muscle strength assessed by knee extension was associated with a lower risk of developing a meningioma in the adjusted analyses (RR 0.5, 95% CI 0.2‐1.0, p = 0.04 for quartiles 3‐4 vs. 1). No other lifestyle‐associated variable was associated with subsequent meningioma. Conclusion Independent of cranial radiation, muscle strength was associated with a lower risk of developing a subsequent meningioma in childhood cancer survivors.

Key Clinical Message This case report highlights the importance of recognizing and accurately diagnosing ganglioneuroblastoma, an uncommon variant of neuroblastic tumors in children. Ganglioneuroblastomas have diverse clinical and morphological presentations, and histopathological examination is paramount in guiding treatment decisions, especially in cases with ambiguous symptoms. Early detection is crucial, as the prognosis varies significantly based on the subtype and the presence of metastatic disease. Clinicians should maintain a high index of suspicion and utilize radiological examinations to promptly identify and treat these tumors. Abstract Children are frequently affected by neuroblastic tumors, which grow from the sympathoadrenal lineage of the neural crest during its development. However, intermixed ganglioneuroblastomas are far less common within the same tumor spectrum, the diagnosis of which could become challenging amidst an unusual presentation. In our case report, we present a 4‐year‐old boy who had complaints of fever and difficulty in walking, with a supra‐renal mass on ultrasound, which was diagnosed as ganglioneuroblastoma‐intermixed type on histopathological examination. This report aims to contribute to the understanding of the diverse clinical and morphological spectrum of ganglioneuroblastomas and the importance of multidisciplinary collaboration and histopathological examination to enhance decision‐making in such ambiguous scenarios.

Abstract Introduction LANDMARC (CTRI/2017/05/008452), a prospective, observational real‐world study, evaluated the occurrence of diabetes complications, glycemic control and treatment patterns in people with type 2 diabetes mellitus (T2DM) from pan‐India regions over a period of 3 years. Methods Participants with T2DM (≥25 to ≤60 years old at diagnosis, diabetes duration ≥2 years at the time of enrollment, with/without glycemic control and on ≥2 antidiabetic therapies) were included. The proportion of participants with macrovascular and microvascular complications, glycemic control and time to treatment adaptation over 36 months were assessed. Results Of the 6234 participants enrolled, 5273 completed 3 years follow‐up. At the end of 3‐years, 205 (3.3%) and 1121 (18.0%) participants reported macrovascular and microvascular complications, respectively. Nonfatal myocardial infarction (40.0%) and neuropathy (82.0%) were the most common complications. At baseline and 3‐years, 25.1% (1119/4466) and 36.6% (1356/3700) of participants had HbA1c

Abstract With the evolution of the COVID‐19 pandemic, there is now a need for point‐of‐care devices for the quantification of disease biomarkers toward disease severity assessment. Disease progression has been determined as a multifactor phenomenon and can be treated based on the host immune response within each individual. CoST is an electrochemical immunosensor point‐of‐care device that can determine disease severity through multiplex measurement and quantification of spike protein, nucleocapsid protein, D‐dimer, and IL‐2R from 100 μL of plasma samples within a few minutes. The limit of detection was found to be 3 ng/mL and 21 ng/mL for S and N proteins whereas for D‐dimer and IL‐2R it was 0.0006 ng/mL and 0.242 ng/mL, respectively. Cross‐reactivity of all the biomarkers was studied and it was found to be

Abstract Aim To compare factors associated with exclusive breastfeeding (EBF) within 1 h of birth, within 3 days, and within the first 6 months post‐birth. Methods We used multivariate logistic regression models and data from “The Alive and Thrive Phase 2 Amhara Baseline Survey 2015” from Ethiopia (N = 3113). Results Giving colostrum was strongly associated with EBF at all three time points, controlling for multiple confounders. Putting the baby to the breast before cleaning the baby and before cleaning the mother was significantly associated with EBF within 1 h and for the first 3 days. EBF within an hour of birth was more likely for girl babies than boy babies. Having a healthcare professional check whether the baby was sucking well was significantly associated with EBF 3 days post‐birth. Conclusions The World Health Organization recommends breastfeeding within 1 h of birth and exclusively thereafter for 6 months, which can improve health outcomes for infants and children. In Ethiopia, many factors influence breastfeeding practices, but little is known about how these factors differ at various key timepoints in the 6 months after birth. Our study provides important information on correlates of EBF at three timepoints and shows that factors that are significantly correlated with EBF vary over time. Future research should assess the potential causal links among statistically significant associations between EBF and risk factors at various times between birth and 6 months of age. Ultimately, these findings have the potential to inform areas of intervention related to promoting EBF.

Abstract Previous studies have not accounted for the close link between type 2 diabetes mellitus (T2DM) and obesity when investigating the impact of T2DM on cytochrome P450 (CYP) activities. The aim was to investigate the effect of T2DM on in vivo activities and protein expressions of CYP2C19, CYP3A, CYP1A2, and CYP2C9 in patients with obesity. A total of 99 patients from the COCKTAIL study (NCT02386917) were included in this cross‐sectional analysis; 29 with T2DM and obesity (T2DM‐obesity), 53 with obesity without T2DM (obesity), and 17 controls without T2DM and obesity (controls). CYP activities were assessed after the administration of a cocktail of probe drugs including omeprazole (CYP2C19), midazolam (CYP3A), caffeine (CYP1A2), and losartan (CYP2C9). Jejunal and liver biopsies were also obtained to determine protein concentrations of the respective CYPs. CYP2C19 activity and jejunal CYP2C19 concentration were 63% (−0.39 [95% CI: −0.82, −0.09]) and 40% (−0.09 fmol/μg protein [95% CI: −0.18, −0.003]) lower in T2DM‐obesity compared with the obesity group, respectively. By contrast, there were no differences in the in vivo activities and protein concentrations of CYP3A, CYP1A2, and CYP2C9. Multivariable regression analyses also indicated that T2DM was associated with interindividual variability in CYP2C19 activity, but not CYP3A, CYP1A2, and CYP2C9 activities. The findings indicate that T2DM has a significant downregulating impact on CYP2C19 activity, but not on CYP3A, CYP1A2, and CYP2C9 activities and protein concentrations in patients with obesity. Hence, the effect of T2DM seems to be isoform‐specific.

ABSTRACT Importance During the coronavirus disease 2019 (COVID‐19) lockdown, changes in the visiting rules in neonatal units might have affected the initiation and continuation of breastfeeding. Objective To investigate the effects of the implementation of the COVID‐19 lockdown in the UK on mother's own milk (MOM) feeding in hospital and at the time of discharge in two UK neonatal units. Methods Retrospective cohort study using routinely recorded data from electronic patient records. Data were retrieved from two neonatal services in the UK East Midlands region. Adjusted logistic regression was used to compare the odds of MOM feeding before, and after the implementation of the UK lockdown. Results Among 2073 infants, after adjusting for maternal and infant characteristics and underlying trends over time, there were no differences in the odds of infants receiving any MOM during admission; any MOM at discharge or exclusive MOM at discharge before and after the imposition of the lockdown. Infants with birthweight 2500 g (adjusted odds ratio [OR] 0.33, 95% confidence interval [CI]: 0.22–0.50). Younger mothers were less likely, and Black British mothers more likely, to be feeding MOM to their infants at discharge, while women in the least deprived Index of Multiple Deprivation (IMD) quintiles were 2–4 times more likely to do so, compared to those in the most deprived IMD quintile (adjusted OR 2.78, 95% CI: 1.97–3.90). Interpretation Despite the difficulties faced during COVID‐19 pandemic‐induced restrictions, infants in the participating neonatal units continued to receive MOM in similar proportions as before the pandemic.

Abstract Agricultural development projects increasingly aim to improve health and nutrition outcomes, often by engaging women. Although evidence shows such projects can improve women's and children's health and nutrition and empower women, little is known about their impacts on women's health‐ and nutrition‐related agency and the extent to which impacts emerge through women's empowerment, largely due to a lack of instruments that measure the dimensions of women's agency that are directly relevant to health and nutrition outcomes. We developed an optional, complementary module for the project‐level women's empowerment in agriculture index (pro‐WEAI) to measure health‐ and nutrition‐related agency (pro‐WEAI + HN). Our method for developing related indicators used data collected from six agricultural development programmes implemented across Bangladesh, Burkina Faso and Mali (pooled sample = 12,114) and applied psychometric analysis (exploratory and confirmatory factor analysis) and the Alkire−Foster methodology. Results revealed seven indicators covering women's agency in the areas of her own health and diet; her health and diet during pregnancy; her child's diet; breastfeeding and weaning; purchasing food and health products; and acquiring food and health products. Multigroup confirmatory factor analysis revealed measurement invariance across contexts and samples. Tests of association (Cramer's V) and redundancy suggest that the pro‐WEAI + HN indicators measured aspects of agency that are distinct from the core pro‐WEAI. The uptake of these indicators in studies of nutrition‐sensitive agricultural development projects may strengthen the evidence on how such programming can enhance women's empowerment to improve health and nutrition outcomes for themselves and their children.

Abstract Objective Breast cancer survivors (BCS) are twice as likely to report symptoms of poor sleep as those without cancer. However, sleep disorders are under‐assessed and under‐treated among BCS. The purpose of this study was to determine the portion of BCS who completed referral visits to a sleep specialist and identify the acceptability, facilitators, and barriers to the screening and referral process. Methods BCS, who reported having sleep problems, completed questionnaires to screen for symptoms suggestive of sleep disorders. Those with symptoms suggestive of sleep apnea, movement disorders, narcolepsy, insomnia syndrome, or circadian disorders, they were referred to a sleep medicine physician or behavioral sleep medicine psychologist. Two months after the referral, participants were interviewed about their perceptions of the acceptability, barriers, and facilitators to sleep screenings and referrals. Results Of 34 BCS assessed for eligibility, 29 were eligible and had sleep problems. Only eight of 29 participants (27.6%) completed the sleep referral process. Most thought the screening and referral process was acceptable. However, BCS identified barriers to completing the referral visit, including time, not seeing the need for treatment, insurance/sick leave concerns, and distance/transportation. Conclusion Adequate evaluation and treatment of sleep disorders in BCS are rare. Creative solutions to address barriers to timely sleep referrals are needed to reduce long‐term negative consequences of inadequate sleep.

Abstract Introduction There are limited data on the real‐world management of diabetes in the Indian population. In this 2‐year analysis of the LANDMARC study, the management of type 2 diabetes mellitus (T2DM) and related complications were assessed. Method This multicenter, observational, prospective study included adults aged ≥25 to ≤60 years diagnosed with T2DM (duration ≥2 years at enrollment) and controlled/uncontrolled on ≥2 anti‐diabetic agents. This interim analysis at 2 years reports the status of glycaemic control, diabetic complications, cardiovascular (CV) risks and therapy, pan‐India including metropolitan and non‐metropolitan cities. Results Of the 6234 evaluable patients, 5318 patients completed 2 years in the study. Microvascular complications were observed in 17.6% of patients (1096/6234); macrovascular complications were observed in 3.1% of patients (195/6234). Higher number of microvascular complications were noted in patients from non‐metropolitan than in metropolitan cities (p

Abstract In this work, we propose a novel diagnostic workflow—DigEST—that will enable stratification of disease states based on severity using multiplexed point of care (POC) biosensors. This work can boost the performance of current POC tests by enabling clear, digestible, and actionable diagnoses to the end user. The scheme can be applied to any disease model, which requires time‐critical disease stratification for personalized treatment. Here, urinary tract infection is explored as the proof‐of‐concept disease model and a four‐class classification of disease severity is discussed. Our method is superior to traditional enzyme‐linked immunosorbent assay (ELISA) as it is faster and can work with multiple disease biomarkers and categorize diseases by endotypes (or disease subtype) and severity. To map the nonlinear nature of biochemical pathways of complex diseases, the method utilizes an established supervised machine learning model for digital classification. This scheme can potentially boost the diagnostic power of current electrochemical biosensors for better precision therapy and improved patient outcomes.

Abstract Background Patients undergoing limb amputation (LA) or limb‐sparing (LS) for lower extremity oncologic diagnoses are at similar risk for chronic postsurgical pain of neuropathic nature (CPSP/NP). Regional anesthesia (RA) techniques are pre‐emptive measures to prevent the occurrence of the CPS/NP. However, recommendations for epidural (EP) versus peripheral nerve blocks (PNBs) lack in pediatric literature. Aims This study investigates the incidence and duration of CPSP/NP and describes NP‐directed regimens. Methods and Results Data on demographics, use of EP or PNB, duration of CPSP/NP, and NP‐directed medication were retrospectively collected for LA and LS between 2009 and 2019. Mixed effects logistic regression was used to compare the odds of CPSP/NP between EP and PNB. Cox PH model with adjustment for clustering due to multiple surgeries on patients was used to quantify rate of pain relief between surgery groups (LA vs. LS) and RA groups (EP vs. PNB). The incidence of CPSP/NP was 36 (23.8%) after 165 surgeries (150 patients). The odds of CPSP/NP after PNB were 2.5 times those of CPSP/NP after EP (p = .11). The rate of pain relief at any instant after the EP was 1.2 times that after PNB (p = .3). The rate of pain relief for LS with EP was 1.9 times that of pain relief for LA with EP, a statistically significant difference (p = .03). Gabapentin was used (94.5%), with addition of amitriptyline (24.2%) and both amitriptyline and methadone (12.7%). Conclusion The LS with the EP group had a significantly higher rate of relief of CPSP/NP than LA with EP. Odds of CPSP/NP after PNB were 2.5 times those of CPSP after EP.

Erythema multiforme (EM) is an acute inflammatory, mucocutaneous, psychosomatic, and vesiculobullous condition that varies from minor to major forms. The acral distribution of target lesions is a characteristic of this condition. The aetiology of erythema multiforme is multifactorial. 90% of the cases are triggered by a herpes infection, whereas 10% occur secondary to drug intake. The offending drugs include nonsteroidal anti-inflammatory drugs, antibiotics, and anticonvulsants. The present case series discusses four cases of drug-induced erythema multiforme and their management.

Cerebritis and infective endocarditis caused by Listeria monocytogenes are very rare. A 56-year-old man presented with slurring of speech and generalized body weakness of 1 week duration. He did not have any past medical history. On systemic examination, he had mild slurring of speech and facial asymmetry and was initially treated for multifocal chronic cerebral infarcts. Listeria monocytogenes was isolated from blood culture on day 5 of admission. A diagnosis of neurolisteriosis was made as contrast-enhanced-computed tomography (CECT) of the brain showed right frontal cerebritis. He was treated with intravenous benzyl penicillin. His general condition was improving until day 13 of hospitalization whereby he developed haemoptysis and severe Type 1 respiratory failure requiring reintubation. An urgent transthoracic echocardiogram revealed a large vegetation at the anterior mitral valve leaflet measuring 2.01 cm. No active arterial bleeding was seen on computed tomography angiography (CTA) of the thorax. Magnetic resonance imaging (MRI) of the brain showed evidence of right frontal cerebritis. He continued to deteriorate and succumbed to his illness after 3 weeks of hospitalization. Clinicians should be aware of such an occurrence and prompt recognition and adequate treatment are necessary in cases of Listeria monocytogenes cerebritis and infective endocarditis as both are deadly entities.

Background Cerebral venous thrombosis is a devastating condition with, despite optimal medical management, a significant proportion deteriorating due to involvement of the deep venous system, worsening intracranial pressures, and hemorrhage. In this study, we report the characteristics, immediate and long‐term outcomes of mechanical thrombectomy (MT) using a Forgarty balloon catheter among patients with cerebral venous thrombosis. Methods A prospective study conducted at the Christian Medical College, Vellore over 5 years (February 2017–February 2022), wherein patients with cerebral venous thrombosis who had clinical deterioration despite best medical management and requiring MT were included. MT was performed through retrograde venous access through internal jugular veins using a Fogarty balloon. The primary outcome was composite end point of mortality and proportion of patients with favorable clinical response at last follow‐up, defined as a disability score in modified Rankin scale 0–2. Results Among 546 patients treated in our center during the study period, 57(10%), patients required MT. The median age of the study population was 33 years (interquartile range: 17–70 years) with equal gender predilection. Hemorrhagic venous infarction was seen in 28/57 (50%) patients. The mean duration between starting medical treatment and to MT was 43 hours (interquartile range: 5–260 hours) with the most common indication being clinical deterioration (70%). Five patients (9%) required decompressive hemicraniectomy. The mortality at discharge was 5% (n=3), and at last follow‐up visit was 7% (n=4). Younger patients without hemorrhagic venous infarction and non‐involvement of the frontoparietal lobes seem to benefit the most. Favorable functional outcome at discharge (modified Rankin scale 0–2) was seen in 65% which further improved to 77% at 1‐year follow‐up. Conclusion Balloon‐assisted MT is safe and effective in a subset of patients with severe cerebral venous thrombosis, with clinical deterioration despite optimal medical management.

Abstract It remains uncertain whether pharmacokinetic changes following Roux‐en‐Y gastric bypass (RYGB) can be attributed to surgery‐induced gastrointestinal alterations per se and/or the subsequent weight loss. The aim was to compare short‐ and long‐term effects of RYGB and calorie restriction on CYP3A‐activity, and cross‐sectionally compare CYP3A‐activity with normal weight to overweight controls using midazolam as probe drug. This three‐armed controlled trial included patients with severe obesity preparing for RYGB (n = 41) or diet‐induced (n = 41) weight‐loss, and controls (n = 18). Both weight‐loss groups underwent a 3‐week low‐energy‐diet (

Abstract Epilepsy is one of the most common neurological disorders; it affects millions of people globally. Because of the risks to health that it causes, the study and analysis of epilepsy have been given considerable attention in the biomedical field. In a neurological diagnosis, an automated device for detecting seizures or epilepsy from an electroencephalogram (EEG) signal has a significant role. This research work proposes a very large scale integration implementation system for the automatic detection of seizures. Before classification, feature extraction was performed by discrete wavelet transform (DWT) and on‐chip classification was performed by a linear support vector machine. The polyphase architecture of Daubechies fourth‐order wavelet three‐level DWT was used to minimize computational time. The systolic array architecture‐based support vector machine classifier using parallel processing helps to minimize the computational complexity of the proposed method. This research work uses an open access EEG dataset. Hardware implementation was done on a field‐programmable gate array (FPGA). Efficient results were produced compared with the existing system on chip (SoC) and FPGA seizure detection systems.

Abstract Exome sequencing (ES) has revolutionized rare disease management, yet only ~25%–30% of patients receive a molecular diagnosis. A limiting factor is the quality of available phenotypic data. Here, we describe how deep clinicopathological phenotyping yielded a molecular diagnosis for a 19‐year‐old proband with muscular dystrophy and negative clinical ES. Deep phenotypic analysis identified two critical data points: (1) the absence of emerin protein in muscle biopsy and (2) clinical features consistent with Emery‐Dreifuss muscular dystrophy. Sequencing data analysis uncovered an ultra‐rare, intronic variant in EMD, the gene encoding emerin. The variant, NM_000117.3: c.188‐6A > G, is predicted to impact splicing by in silico tools. This case thus illustrates how better integration of clinicopathologic data into ES analysis can enhance diagnostic yield with implications for clinical practice.