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Objective: Recessive variants in the PINK1 gene are known causes of early-onset Parkinson's disease (EOPD). To describe the clinical features and genetic profiles of patients with PINK1-related Parkinson's disease (PARK-PINK1) mutations., Methods: We conducted a retrospective chart review of the demographic, clinical and genetic details of patients from our database carrying biallelic PINK1 variants., Results: A total of 7 patients whose median age at onset was 33 years (range: 20-49) were recruited. All had asymmetrical onset, tremors were present in 4 patients, abnormal posturing was present in 2 patients, and slowness was present in 1 patient. The parkinsonism phenotype was noted in 6 patients (with dystonia in four) and isolated dystonia in one. Among the 6 patients with parkinsonism, five had rest tremors, all had good levodopa responses, and four had motor fluctuations with choreiform dyskinesia. Exome sequencing revealed biallelic pathogenic/likely pathogenic variants, five of which were novel., Conclusion: PARK-PINK1 presents as an EOPD with tremor-predominant phenotype, good levodopa-responsiveness, early motor fluctuation and dyskinesia. We describe five novel variants in PINK1 gene.

Introduction: Indian Parkinson's Disease (PD) patients are severely underrepresented in terms of genetic studies and little is known about the frequency of variants and their impact on motor and nonmotor symptoms (NMS)., Methods: This retrospective cross-sectional study was conducted in PD patients undergoing treatment at a tertiary care hospital from India. Patients were advised genetic testing if they had (i) age at onset (AAO) of motor symptoms at or before 50 years (EOPD), (ii) positive family history of PD, parkinsonism or dystonia. All patients underwent whole exome sequencing and potentially pathogenic variants were identified., Results: Clinical and genetic data were available for 230 (163 males, 70.4 %) patients. Thirty-five pathogenic and likely pathogenic variants in various PD genes were identified in 47 patients resulting in a yield of 20.4 %. In the remaining, 82 patients had either variants of uncertain significance or had variants in genes not associated with parkinsonism and 101 patients did not have any non-benign variants. Patients with genetically mediated PD had a lower AAO and statistically greater frequency of dystonia (36.2 %), postural instability (29.8 %) and mood disorder (29.8 %) and a higher Hoehn and Yahr score (2.9). Among the 47 patients, 11 patients had PARK-PRKN, six patients had PARK-PLA2G6, and 22 patients had PARK-GBA1., Conclusion: Around one-fifth of early-onset PD can have an underlying monogenetic cause. PARK-GBA1, PARK-PRKN and PARK-PLA2G6 are the commoner causes of genetically mediated PD in India. Patients with genetic cause had an earlier age at onset, and more frequent dystonia, postural instability and dyskinesia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Pal has received research grants given to the Institute from the Indian Council of Medical Research (ICMR), Department of Biotechnology (DBT), Scientific Knowledge for Ageing and Neurological ailments (SKAN) Research Trust, India and Michael J. Fox Foundation and honoraria from the International Parkinson and Movement Disorder Society, and Movement Disorder Societies of Korea, Taiwan and Bangladesh and Japanese Society of Neurology for invited lectures and honorarium from Teva-Lundbeck for review article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The present work investigates the structural and luminescence behaviour of Dy 3+ -Sm 3+ co-doped glass ceramics obtained through heat treatment of precursor glasses. The growth of SiO 2 polycrystalline particles and evolution of these crystallites in the glass domain are witnessed via XRD and FESEM study. The presence of network vibrational bands, hydroxyl groups and the increased quantity of bridging oxygens (BOs) in glass ceramics are analysed through FTIR spectroscopy study. The absorption study (UV-Visible-NIR) showed the possible electronic transitions of Dy 3+ and Sm 3+ ions. The red shift in the absorption band edges and the lower bandgap values are obtained as a result of improved heat treatment in glass ceramics. Emission studies show the enhanced luminescence intensity of glass ceramics under 350 and 402 nm excitations. Decay measurement of glass ceramics showed the improved lifetimes of Dy 3+ and Sm 3+ ions to have appeared in microseconds (×10 -6  s). The colour characteristics of glass ceramics analysed using CIE colour chromaticity diagram and correlated colour temperature (CCT) values suggest the neutral to cool white light emissions. Therefore, prepared glass ceramics with SiO 2 polycrystalline phase are considered to be suitable materials in cool white LEDs applications., (© 2024 The Author(s). Luminescence published by John Wiley & Sons Ltd.)

Purpose: Early-onset biliary tract cancer (eoBTC) is among the fast-growing subset of early-onset cancers, yet little is known about its biology. We sought to identify novel molecular characteristics of eoBTC in relation to average-onset BTC (aoBTC) using a real-world multiomics data set., Methods: The study comprised patients with BTC whose tumors underwent molecular analyses at Caris Life Sciences and were categorized by age (<50 years for eoBTC, ≥50 years for aoBTC). P values were adjusted for multiple testing and considered significant at Q < 0.05 (molecular comparisons) or Q < 0.25 (Gene Set Enrichment Analysis [GSEA]). Insurance claims data were used for survival analysis., Results: The study included 5,587 patients with BTC (453 eoBTC, median age = 44 years and 5,134 aoBTC, median age = 68 years). FGFR2 fusion (15.7% in eoBTC v 5.9% in aoBTC) and NIPBL fusion (1.1% v 0%) were significantly more prevalent in eoBTC (both Q < 0.001). The interferon gamma-IFG score (fold change [FC], 1.1; Q = 0.01) and T-cell inflammation score (FC, 17.3; Q = 0.03) were significantly higher in aoBTC. On GSEA, angiogenesis was enriched in eoBTC (normalized enrichment score [NES] = 1.51; Q = 0.16), whereas IFG (NES = -1.58; Q = 0.06) and inflammatory response (NES = -1.46; Q = 0.18) were enriched in aoBTC. The median overall survival (OS) was 16.5 (eoBTC) versus 13.3 months (aoBTC), hazard ratio = 0.86, P = .004. The median OS by FGFR2 fusion (with fusion v without) was 21.7 versus 15.0 months ( P = .47) for eoBTC and 18.6 versus 12.2 months ( P < .001) for aoBTC., Conclusion: We identified crucial differences including higher prevalence of FGFR2 fusions in eoBTC and variations in immunotherapy-related markers. Better outcomes in eoBTC were affected by the FGFR2 fusion status. Our findings underscore the need for ensuring access to next-generation sequencing testing, including prompt identification of actionable targets.

Scope: Edible insect proteins are increasingly introduced as an alternative sustainable food source to address the world's need to feed the growing population. Tropomyosin is the main insect allergen; however, additional potential allergens are not well characterized and the impact of extraction procedures on immunological reactivity is unknown., Methods and Results: Proteins from different commercial food products derived from cricket (Acheta domesticus) and black soldier fly (BSF) (Hermetia illucens) are extracted using five different extraction buffers. The proteins are analyzed by SDS-PAGE and immunoblotting using allergen-specific antibodies and crustacean allergic patient sera. IgE binding bands are analyzed by mass spectrometry as well as the complete allergen profile of all 30 extracts. Urea-based buffers are most efficient in extracting insect allergens. Shrimp-specific antibody cross-reactivity to tropomyosin from cricket and BSF indicates high sequence and structural similarity between shrimp and insects. Additional unique allergens are identified in both species, including hemocyanin, vitellogenin, HSP20, apolipophorin-III, and chitin-binding protein., Conclusions: Identifying potential allergenic proteins and their isoforms in cricket and BSF requires specific extraction approaches using urea-based methods. While tropomyosin is the most abundant and immunoreactive allergen, seven unique allergens are identified, highlighting the need for insect species-specific allergen detection in food products., (© 2024 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

The incidence of bacterial infections is high in patients with liver cirrhosis (LC) due to compromised immune systems. They are associated with acute hepatic decompensation, multiorgan dysfunction, high morbidity, and mortality and account for 25-46% of all hospitalizations. The mortality rate is about 30% after one month and increases to 63% at one-year follow-up. While spontaneous bacterial peritonitis (SBP), urinary tract infections, soft tissue infections, and respiratory tract infections (pneumonia) are some of the common infections, SBP accounts for 25-31% of the cases and is the most frequent bacterial infection. Impaired activity of the phagocytes of the reticuloendothelial system, decreased production of the complement, and bacteria gaining access into the systemic circulation through the porto-systemic shunts are some of the causes of high-risk bacterial infection in patients with LC. The diagnosis of bacterial infection may be challenging as the typical symptoms like fever may not always be evident. We present a very challenging, middle-aged patient of cirrhosis with diabetes mellitus (DM) who presented with infections at multiple sites like SBP due to Serratia ficaria, multiple pyemic liver abscesses, left peri-nephric abscess with septicaemia, further complicated by portal vein thrombosis - all during single hospital admission. SBP was unique in the sense that no case of SBP due to Serratia ficaria has been published in the literature to date. The stormy clinical course, management, and outcome of the patient are described here., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kamath et al.)

The incidence of early-onset colorectal cancer (eoCRC) is rising, and its pathogenesis is not completely understood. We hypothesized that machine learning utilizing paired tissue microbiome and plasma metabolome features could uncover distinct host-microbiome associations between eoCRC and average-onset CRC (aoCRC). Individuals with stages I-IV CRC (n = 64) were categorized as eoCRC (age ≤ 50, n = 20) or aoCRC (age ≥ 60, n = 44). Untargeted plasma metabolomics and 16S rRNA amplicon sequencing (microbiome analysis) of tumor tissue were performed. We fit DIABLO (Data Integration Analysis for Biomarker Discovery using Latent variable approaches for Omics studies) to construct a supervised machine-learning classifier using paired multi-omics (microbiome and metabolomics) data and identify associations unique to eoCRC. A differential association network analysis was also performed. Distinct clustering patterns emerged in multi-omic dimension reduction analysis. The metabolomics classifier achieved an AUC of 0.98, compared to AUC 0.61 for microbiome-based classifier. Circular correlation technique highlighted several key associations. Metabolites glycerol and pseudouridine (higher abundance in individuals with aoCRC) had negative correlations with Parasutterella, and Ruminococcaceae (higher abundance in individuals with eoCRC). Cholesterol and xylitol correlated negatively with Erysipelatoclostridium and Eubacterium, and showed a positive correlation with Acidovorax with higher abundance in individuals with eoCRC. Network analysis revealed different clustering patterns and associations for several metabolites e.g.: urea cycle metabolites and microbes such as Akkermansia. We show that multi-omics analysis can be utilized to study host-microbiome correlations in eoCRC and demonstrates promising biomarker potential of a metabolomics classifier. The distinct host-microbiome correlations for urea cycle in eoCRC may offer opportunities for therapeutic interventions., (© 2024. The Author(s).)

Ultra-high thermally stable Ca 2 MgWO 6 :xSm 3+ (x = 0.5, 0.75, 1, 1.25, and 1.5 mol%) double perovskite phosphors were synthesized through solid-state reaction method. Product formation was confirmed by comparing the X-ray diffraction (XRD) patterns of the phosphors with the standard reference file. The structural, morphological, thermal, and optical properties of the prepared phosphor were examined in detail using XRD, Fourier transform infrared spectra, scanning electron microscopy, diffused reflectance spectra, thermogravimetric analysis (TGA), photoluminescence emission, and temperature-dependent PLE (TDPL). It was seen that the phosphor exhibited emission in the reddish region for the near-ultraviolet excitation with moderate Colour Rendering Index values and high colour purity. The optimized phosphor (x = 1.25 mol%) was found to possess a direct optical band gap of 3.31 eV. TGA studies showed the astonishing thermal stability of the optimized phosphor. Additionally, near-zero thermal quenching was seen in TDPL due to elevated phonon-assisted radiative transition. Furthermore, the anti-Stokes and Stokes emission peaks were found to be sensitive toward the temperature change and followed a Boltzmann-type distribution. All these marked properties will make the prepared phosphors a suitable candidate for multifield applications and a fascinating material for further development., (© 2024 John Wiley & Sons Ltd.)

Due to the widespread use of shellfish ingredients in food products, accurate food labelling is urgently needed for consumers with shellfish allergies. Most crustacean allergen detection systems target the immunorecognition of the allergenic protein tropomyosin. However, this mode of detection may be affected by an origin-dependent protein composition. This study determined if the geographic location of capture, or aquaculture, influenced the allergenic protein profiles of Black Tiger Shrimp ( Penaeus monodon ), one of the most farmed and consumed shrimp species worldwide. Protein composition was analysed in shrimp from nine different locations in the Asia-Pacific by SDS-PAGE, immunoblotting, and mass spectrometry. Ten of the twelve known shrimp allergens were detected, but with considerable differences between locations. Sarcoplasmic calcium-binding protein, myosin light chain, and tropomyosin were the most abundant allergens in all locations. Hemocyanin-specific antibodies could identify up to six different isoforms, depending on the location of origin. Similarly, tropomyosin abundance varied by up to 13 times between locations. These findings suggest that allergen abundance may be related to shrimp origin and, thus, shrimp origin might directly impact the readout of commercial crustacean allergen detection kits, most of which target tropomyosin, and this should be considered in food safety assessments.

Purpose: National Cancer Institute (NCI) and nonprofit organization (NPO) funding is critical for research and advocacy but may not be equitable across cancers., Methods: This study evaluated funding from the NCI and NPOs supporting lung, breast, colorectal, pancreatic, hepatobiliary, prostate, ovarian, cervical and endometrial cancers, leukemia, lymphoma, and melanoma from 2015 to 2018. The primary objectives were to assess for funding disparities across different cancers compared with their incidence and mortality and across racial groups. We also determined if underfunding correlates with fewer clinical trials. Correlations between funding for each cancer and its incidence, mortality, and number of clinical trials were analyzed using descriptive statistics and Pearson correlation coefficients (CCs)., Results: Diseases with the largest combined NCI and NPO funding were breast cancer ($3.75 billion in US dollars [USD]) and leukemia ($1.99 billion USD). Those with the least funding were endometrial ($94 million USD), cervical ($292 million USD), and hepatobiliary cancers ($348 million USD). Disease-specific funding correlated well with incidence but correlated poorly with mortality (Pearson CCs, 0.74; P = .006 and .30, P = .346, respectively). Breast cancer, leukemia, and lymphoma were well-funded while colorectal, lung, hepatobiliary and uterine cancers were underfunded. Higher incidence among Black patients correlated with underfunding. The amount of funding for a particular cancer correlated strongly with the number of clinical trials for that disease (Pearson CC, 0.91; P < .0001)., Conclusion: Many cancers with high incidence and mortality rates are underfunded. Cancers that affect Black patients at higher rates are also underfunded. Underfunding strongly correlates with fewer clinical trials, which could impede future advances in underfunded cancers.

Opinion Statement: Neoadjuvant chemotherapy is safe for patients with locally advanced colon cancer (LACC). The FOxTROT trial demonstrated a reduction in residual and recurrent cancer at 2 years with neoadjuvant chemotherapy for patients with cT3-4 LACC. Preoperative chemotherapy should be avoided, if possible, for patients with dMMR LACC, as over 50% of dMMR cancers have no pathologic response. Early universal testing of MMR status is critical to selecting the appropriate neoadjuvant therapy. Concerns about CT staging of LACC have limited uptake of neoadjuvant chemotherapy, as approximately 25% of patients with cT3-T4 cancer on CT have low-risk stage II disease. Development of CT criteria for malignant nodes should reduce the risk of over-staging. A multidisciplinary approach is needed to identify patients for neoadjuvant therapy. Neoadjuvant immunotherapy is safe and results in dramatic pathologic responses in patients with dMMR LACC. Longer follow-up is needed to determine if the exceptionally high pathologic response rates observed will translate into long-term remission. Remarkably, neoadjuvant immunotherapy has been found to cause major pathologic responses in a subset of patients with pMMR LACC, indicating the potential to cure more patients with this common cancer. Patients with cT4 LACC, whether stage II or III, have a substantial risk of recurrence despite adjuvant fluoropyrimidine plus oxaliplatin chemotherapy. We recommend neoadjuvant systemic therapy for all patients with cT4b LACC (dMMR and pMMR). Features of T4b disease are routinely reported by radiology. We use three cycles of FOLFOX chemotherapy for patients with cT4b pMMR LACC, due to the high rate of compliance and improvement in residual and recurrent disease. Patients with cT4b dMMR LACC should receive neoadjuvant immunotherapy, if there are no contraindications. Clinical trials of neoadjuvant therapy for LACC are of great interest and should provide training for radiologists to identify eligible patients. Results are anticipated from multiple ongoing trials of neoadjuvant chemotherapy, immunotherapy, and targeted therapy for pMMR LACC and immunotherapy for dMMR LACC., (© 2024. The Author(s).)

Deleterious effects of environmental exposures may contribute to the rising incidence of early-onset colorectal cancer (eoCRC). We assessed the metabolomic differences between patients with eoCRC, average-onset CRC (aoCRC), and non-CRC controls, to understand pathogenic mechanisms. Patients with stage I-IV CRC and non-CRC controls were categorized based on age ≤ 50 years (eoCRC or young non-CRC controls) or  ≥ 60 years (aoCRC or older non-CRC controls). Differential metabolite abundance and metabolic pathway analyses were performed on plasma samples. Multivariate Cox proportional hazards modeling was used for survival analyses. All P values were adjusted for multiple testing (false discovery rate, FDR P < 0.15 considered significant). The study population comprised 170 patients with CRC (66 eoCRC and 104 aoCRC) and 49 non-CRC controls (34 young and 15 older). Citrate was differentially abundant in aoCRC vs. eoCRC in adjusted analysis (Odds Ratio = 21.8, FDR P = 0.04). Metabolic pathways altered in patients with aoCRC versus eoCRC included arginine biosynthesis, FDR P = 0.02; glyoxylate and dicarboxylate metabolism, FDR P = 0.005; citrate cycle, FDR P = 0.04; alanine, aspartate, and glutamate metabolism, FDR P = 0.01; glycine, serine, and threonine metabolism, FDR P = 0.14; and amino-acid t-RNA biosynthesis, FDR P = 0.01. 4-hydroxyhippuric acid was significantly associated with overall survival in all patients with CRC (Hazards ratio, HR = 0.4, 95% CI 0.3-0.7, FDR P = 0.05). We identified several unique metabolic alterations, particularly the significant differential abundance of citrate in aoCRC versus eoCRC. Arginine biosynthesis was the most enriched by the differentially altered metabolites. The findings hold promise in developing strategies for early detection and novel therapies., (© 2024. The Author(s).)

In this work, copper (Cu)-doped titanium dioxide (TiO2) nanoparticles were prepared by co-precipitation. For studying the morphological properties, the copper doped titanium dioxide (TiO2:Cu) nanocrystalline structures were characterised through powder X-ray diffraction and field emission scanning electron microscopy. The prepared TiO2:Cu nanoparticles were annealed at two temperatures, namely, copper doped titanium dioxide annealed at 723 K temperayure (TC1) and copper doped titanium dioxide annealed at 1073 K temperayure (TC2). The annealed samples were exposed to gamma radiation of 10-Gy-to-25-kGy doses. Thermoluminescence and dosimetric properties were evaluated using a thermoluminescent dosemeter reader. The glow curves of the TiO2:Cu nanoparticles were analysed. The thermoluminescence (TL) response of samples exhibited good linearity between 100 Gy and 10 kGy with high sensitivity of 1755.25 (TC1) and 5587.06 (TC2) counts g-1Gy-1 and a minimum detectable dose of 2.9666 Gy (TC1) and 0.4892 Gy (TC2). The fading of signals was observed by 12% for TC1 and 10% for TC2 samples after a week of storage., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Genetic literacy refers to an individual's ability to understand the basics of genetic concepts and apply them to health-related decisions. The level of genetic literacy influences attitude towards genetic testing and is, in turn, influenced by several other factors. Clinicians must be aware of the genetic literacy of their patients and their caregivers before advising genetic testing and/or undertaking pre and post-test counseling., Method: A systematic review of literature in PubMed was carried out using keywords "Genetic testing", "Genetic counseling", "Knowledge", "Attitude", "Parkinson's disease" in various combinations., Results: Seven eligible studies with a total of 1837 individuals (patients with PD-1355 and patient caregivers-482) were identified. More than half the participants were well-versed in basic concepts of genetics (57.8%) and risks of inheriting PD (60.5%) while less than 10% were aware regarding the contribution of specific genes (e.g. LRRK2). Interest in diagnosis, treatment, prevention and facilitating PD research were central themes for positive attitude while apprehensions revolving around impact on employment and insurance and non-benefit were associated with negative attitudes. Possible associations included greater knowledge scores with positive attitudes towards genetic testing and older age for negative attitude towards testing. Insufficient data on attitudes toward prenatal testing, presymptomatic testing and clinicians' attitude toward testing was identified., Conclusion: Patients with PD and their caregivers are aware of the role of genetics in the etiopathogenesis of their disease, which contributes to their positive attitude towards testing. Further studies exploring negative attitudes towards testing will help overcome the hurdles in genetic testing and counseling in this cohort of patients., Competing Interests: Declaration of competing interest SK, VVH, NK, RY, and PKP have no financial disclosures or any conflicts of interest to report relevant to this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Competing Interests: There are no conflicts of interest.

Introduction Japanese encephalitis (JE), caused by a Flavivirus , is one of the common causes of mosquito-borne encephalitis the world over including India. The disease is endemic in many states of India, including Jharkhand. Mortality ranges from 30 to 40% in different studies and a large number of patients survive with permanent neuropsychiatric sequelae. Aim The study aimed to evaluate the clinical spectrum, laboratory (including radiological) features and outcomes of cases of JE admitted in our hospital. Methods and materials This is a retrospective observational study consisting of confirmed cases of JE admitted to the medical wards and critical care unit of Tata Main Hospital (TMH) from January to December 2022. The case records of patients were retrieved from Hospital Management System (HMS) and analysed for demographic characteristics, clinical presentations and treatment details along with outcome measures, which included length of stay (LOS), complications, and mortality. Observation Of the 14 confirmed cases, six (43.9%) were males and eight (57.1%) were females. The average age of male and female patients was 41.8 ± 23.1 and 35.1 ± 20.5 years respectively. A total of 35.7% of the patients were in the age group of 21 to 30 years. The clinical manifestations in the decreasing frequency were altered sensorium in 11 (78.6%) patients, headache in six (42.8%) patients, generalised convulsions in four (28.6%) cases, vomiting in three (21.4%) cases and weakness in all limbs and of the right half of the body in one (7.1%) case each. Objective neurological findings noted were neck stiffness (3, 21.4%), cog-wheel rigidity (3, 21.4%), tremors (2, 14.3%), delirium (2,14.3%), quadriparesis, facio-brachial dystonia and hemiparesis (1, 7.14%) patient each. Neutrophilic leucocytosis was observed in five (35.7%) patients and mild thrombocytopenia in two (14.3%) patients. The average C-reactive protein (CRP) level was 7.3 ± 6.6 mg/dL. Three (21.4%) patients had mild transaminitis. Cerebrospinal fluid analysis was abnormal in all patients with varying degrees of elevated protein and cell count, while adenosine deaminase (ADA) levels and sugar were normal in all patients. Magnetic resonance imaging (MRI) brain revealed bilateral thalamic T2 FLAIR (fluid-attenuated inversion recovery) hyperintensities in 11 patients (78.6%). The average length of hospital stay was 9.6 ± 4.7 days. Ten patients (71.4%) needed treatment in the critical care unit. Complications seen were acute respiratory distress syndrome (2, 14.3%), sepsis with multiorgan failure (2, 14.3%) and ventilator-associated pneumonia (1, 7.1%). The case fatality rate was one (7.1%). Six patients (42.9%) had residual neuropsychiatric sequelae. Conclusion JE continues to be a major health-related problem. Most cases are concentrated during the post-monsoon period, coinciding with a higher vector density. Patients from rural backgrounds were seen to be more susceptible. JE may present with varying severities of acute encephalitic syndrome. As there is no specific treatment, timely diagnosis is important to reduce the morbidity and mortality associated with this disease. Clinicians must be aware of the wide spectrum of presentation of this disease. A high degree of suspicion along with thorough clinical examination and appropriate investigations are needed to diagnose this condition early and prevent complications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kamath et al.)

Allergenic cross-reactivity among food allergens complicates the diagnosis and management of food allergy. This can result in many patients being sensitized (having allergen-specific IgE) to foods without exhibiting clinical reactivity. Some food groups such as shellfish, fish, tree nuts, and peanuts have very high rates of cross-reactivity. In contrast, relatively low rates are noted for grains and milk, whereas many other food families have variable rates of cross-reactivity or are not well studied. Although classical cross-reactive carbohydrate determinants are clinically not relevant, α-Gal in red meat through tick bites can lead to severe reactions. Multiple sensitizations to tree nuts complicate the diagnosis and management of patients allergic to peanut and tree nut. This review discusses cross-reactive allergens and cross-reactive carbohydrate determinants in the major food groups, and where available, describes their B-cell and T-cell epitopes. The clinical relevance of these cross-reactive B-cell and T-cell epitopes is highlighted and their possible impact on allergen-specific immunotherapy for food allergy is discussed., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Young-onset gastrointestinal malignancies appear to be increasing in incidence. There are limited data on young-onset pancreaticobiliary adenocarcinoma (YO-PBA)., Methods: The study comprised patients with PBA (pancreatic adenocarcinoma, intra-, and extra-hepatic cholangiocarcinoma) and included in the National Cancer Database (NCDB) between 2004 and 2017. YO-PBA was defined as a diagnosis at age less than 50 years. Logistic regression to assess factors associated with YO-PBA status, and cox proportional hazards modeling to associate relevant factors with overall survival was performed., Results: The study cohort comprised 360,764 patients, with 20,822 (5.8%) YO-PBA. YO-PBA was associated with (p-values<0.0001 for all): male sex (6.3% YO-male out of all male patients vs. 5.2% YO-female, OR 1.29, 95% CI 1.25-1.33), Black race (7.9% YO-Black vs. 5.0% YO-White, OR 1.72, 95% CI 1.64-1.80), lower income (6.4% YO-lowest household income based group vs. 5.5% highest, OR 1.08, 95% CI 1.03-1.13). YO-PBA were more likely to present with stage-IV disease (6.4% YO-Stage IV of all stage IV vs. 5.4% YO-Stage I-III, OR 1.25, 95% CI 1.21-1.29 p-value < 0.0001). Factors associated with overall survival (OS) in non-operable patients included-sex - male vs. female, HR 1.12 (95% CI 1.08-1.15); race - Black vs. White, HR 1.23 (95% CI 1.06-1.42); income group - lowest vs. highest, HR 1.33 (95% CI 1.27-1.39), and treatment center type - academic vs. nonacademic center, HR 0.87 (95% CI 0.85-0.90)., Conclusions: Socioeconomic factors significantly impact incidence and outcomes for young-onset pancreaticobiliary adenocarcinoma (YO-PBA). More work is needed to help understand the mechanisms involved while addressing the disparities., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Although recent studies indicated that many fish-allergic patients may safely consume certain fish species, no clinical guidelines are available for identification of the exact species tolerated by specific patients., Objective: To investigate whether multiplex immunoglobulin E (IgE) testing reveals potentially tolerated fish through absence of IgE to parvalbumin (PV) and extracts from specific species., Methods: Sera from 263 clinically well-defined fish-allergic patients from Austria, China, Denmark, Luxembourg, Norway, and Spain were used in a research version of the ALEX 2 multiplex IgE quantification assay. Specific IgE to PVs from 10 fish species (9 bony and 1 cartilaginous), and to extracts from 7 species was quantified. The IgE signatures of individual patients and patient groups were analyzed using SPSS and R., Results: Up to 38% of the patients were negative to cod PV, the most commonly used molecule in fish allergy diagnosis. Forty-five patients (17%) tested negative to PVs but positive to the respective fish extracts, underlining the requirement for extracts for accurate diagnosis. Between 60% (Spain) and 90% (Luxembourg) of the patients were negative to PV and extracts from ray, a cartilaginous fish, indicating its potential tolerance. Up to 21% of the patients were negative to at least 1 bony fish species. Of the species analyzed, negativity to mackerel emerged as the best predictive marker of negativity to additional bony fish, such as herring and swordfish., Conclusions: Parvalbumins and extracts from multiple fish species relevant for consumption should be used in fish-allergy diagnosis, which may help identify potentially tolerated species for individual patients., (Copyright © 2022. Published by Elsevier Inc.)

Background: The use of virtual platforms for clinical meetings has become the default approach during this pandemic era. Organising an offline conference during a pandemic is a challenge and is possible if the participating crowd is vaccinated and is willing to follow appropriate pandemic protocols., Objective: To determine the feasibility of conducting a conference among mostly vaccinated delegates using standard precautionary protocols., Methods: This study was conducted at IADVL MIDDERMACON 2021, held in Mangalore, India, in late October 2021, during the phase of decline of the Delta variant of SARS-CoV-2. The study population included all conference attendees, including support staff. Details were collected about their vaccination status, comorbidities, and mode of travel to the conference venue. An reverse-transcription polymerase chain reaction (RT-PCR) test was done randomly among the attendees for COVID-19 infection. A post-conference assessment and RT-PCR tests were done at the end of 2 weeks to assess the occurrence of infections among study participants., Results: A total of 1744 people were present at the venue, of which 576 (33.03%) participated in the study. The percentage of fully vaccinated was 88.88% (512/576). The majority had taken the vaccine Covishield (manufactured by AstraZeneca), that is, 85.06% (490/576). Infection post the conference was reported in 0.195% (1/576)., Conclusions: Holding large gatherings like medical conferences pose a challenge during a pandemic. However, to increase the benefits of the conference, it is advisable to hold them offline with vaccinated delegates, follow the advice of the conference organising committee, and practise safe precautionary measures., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. JEADV Clinical Practice published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for several malignancies. While the use of single-agent or combined ICIs has achieved acceptable disease control rates in a variety of solid tumors, such approaches have yet to show substantial therapeutic efficacy in select difficult-to-treat cancer types. Recently, select chemotherapy regimens are emerging as extensive modifiers of the tumor microenvironment, leading to the reprogramming of local immune responses. Accordingly, data is now emerging to suggest that certain anti-neoplastic agents modulate various immune cell processes, most notably the cross-presentation of tumor antigens, leukocyte trafficking, and cytokine biosynthesis. As such, the combination of ICIs and cytotoxic chemotherapy are beginning to show promise in many cancers that have long been considered poorly responsive to ICI-based immunotherapy. Here, we discuss past and present attempts to advance chemo-immunotherapy in these difficult-to-treat cancer histologies, mechanisms through which select chemotherapies modify tumor immunogenicity, as well as important considerations when designing such approaches to maximize efficacy and improve therapeutic response rates., Competing Interests: Declaration of Competing Interest The authors have no conflicts to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and objective Scrub typhus (ST) is a rickettsial infection caused by Orientia tsutsugamushi , which is transmitted by the bite of the larval stage (chiggers) of trombiculid mites. Although it presents as an acute undifferentiated febrile illness (AUFI), its course can be complicated with acute respiratory distress syndrome, acute kidney injury (AKI), myocarditis, meningoencephalitis, hepatitis, multi-organ dysfunction syndrome (MODS), and ultimately death. This study aimed to evaluate the epidemiological features, clinical profile, laboratory features, and clinical outcomes of cases of scrub typhus and identify the predictors of disease severity. Methods and materials This study is a retrospective observational study that included confirmed cases of scrub typhus admitted in the medical wards and critical care unit (CCU) of Tata Main Hospital (TMH) from January 1, 2019, to December 31, 2021. The case records of patients were analyzed for demographic characteristics, clinical features, treatment, and outcomes, which included length of stay (LOS), complications, and mortality. The required odds ratio (OR) was calculated, univariate and binary regression analyses were done, and a p-value of <0.05 was considered statistically significant. Results Of the 42 confirmed cases, 38.1% were males and 61.9% were females. The average age of male patients was 12.6 ± 11.2 years, while that of females was 22 ± 19.3 years. Of the patients, 64.3% were in the age group of 1-20 years. The clinical manifestations in descending order were fever (71.2%), skin rash (19.1%), cough (16.7%), vomiting (28.6%), altered sensorium (23.8%), abdominal pain (23.8%), loose stools (14.3%), seizures (14.3%), anasarca (9.7%), breathlessness (9.7%), and melena (7.1%). Eschar was noted in 38.1% of patients. Swelling of the body (6.7%) and lymphadenopathy (10%) were seen exclusively in children. The common laboratory abnormalities observed were leukocytosis in 34.3% of cases; thrombocytopenia in 68.8% of cases, of which 25% of patients had platelets < 50,000/mm 3 ; and transaminitis in 87.5% of cases. The ratio of AST/ALT of more than one was seen in 89.3% of patients, while it was less than one in 10.7% of patients. The average C-reactive protein (CRP) level was 10.9 ± 6.3 mg/dL. The complications noted were acute respiratory distress syndrome (ARDS) (16.7%), meningoencephalitis (21.4%), septic shock (14.3%), capillary leak syndrome (26.2%), thrombocytopenia (68.8%), transaminitis (87.5%), myocarditis (4.8%), disseminated intravascular coagulation (2.4%), and hypocalcemia (11.9%). The average length of stay (LOS) was 8.1 ± 4.2 days. Twenty-four (57.2%) patients required transfer to the critical care unit (CCU) for managing various complications. There was no mortality in this series, giving rise to the case fatality ratio (CFR) of 0. Conclusion Scrub typhus is a reemerging cause of acute febrile illness. The highest number of cases were found during the post-monsoon period and in those with rural backgrounds. It presents with varying clinical manifestations with or without eschar. Hence, a high degree of suspicion along with a thorough clinical examination is needed to diagnose this condition. The disease responds dramatically to doxycycline. One must be aware of its complications and atypical presentations, as a timely diagnosis can reduce the morbidity and mortality associated with this disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kamath et al.)

Purpose: The proportion of gastroesophageal junction adenocarcinoma is increasing. This study evaluated trends in early-onset gastric and esophageal cancers and compared socioeconomic and clinical characteristics between early-onset versus late-onset disease., Materials and Methods: We included all patients with gastric and esophageal cancer from 2004 to 2015 from the National Cancer Database. Patients were categorized by age < 50, 50-69, and ≥ 70 years. Differences in pathologic and socioeconomic factors between early-onset and late-onset cancers were assessed by using chi-square test. The effects of demographic and socioeconomic factors on overall survival (OS) were assessed using Cox models., Results: The proportion of patients with early-onset gastric cancer increased from 23.9% in 2004-2006 to 26.2% in 2013-2015, whereas the proportion of early-onset esophageal cancer decreased from 27.3% in 2004-2006 to 23.1% in 2013-2015. For both malignancies, the early-onset group was more likely to be Black or Hispanic and more likely to be diagnosed with stage IV cancer. Black patients had the worst median OS in both malignancies. In gastric cancer, within the Black patient group, patients experienced worse OS if they had government insurance versus private insurance (hazard ratio 1.2; 95% CI, 1.1 to 1.3; P value < .0001) or if they were in the lowest community median income category versus the highest category (hazard ratio 1.2; 95% CI, 1.1 to 1.3; P value < .0001)., Conclusion: Early-onset gastric cancer is increasing, whereas early-onset esophageal cancer is declining. Early-onset gastric cancer disproportionately affects non-White patients, particularly Hispanic patients. Black patients have worse outcomes compared with other races for both gastric and esophageal cancer., Competing Interests: Suneel D. KamathConsulting or Advisory Role: OncLive, Exelixis, TempusTravel, Accommodations, Expenses: AstraZeneca, Bristol Myers Squibb, Merck, Foundation Medicine, Guardant Health, Ipsen, JanssenOpen Payments Link: https://openpaymentsdata.cms.gov/physician/711572/summaryNo other potential conflicts of interest were reported.

Background: Clinical cross-reactivity between bony fish, cartilaginous fish, frog, and chicken muscle has previously been demonstrated in fish-allergic patients. In indicative studies, two reports of anaphylaxis following the consumption of crocodile meat and IgE-cross-binding were linked to the major fish allergen parvalbumin (PV). This study investigates IgE-binding proteins in crocodile meat with a focus on PV and their clinical relevance., Methods: Proteins were extracted from muscle tissue of crocodile, three bony fish, and two cartilaginous fish. A cohort of fish-allergic pediatric patients (n = 77) underwent allergen skin prick testing (SPT) to three fish preparations (n = 77) and crocodile (n = 12). IgE-binding proteins were identified and quantified by SDS-PAGE, mass spectrometric analyses, and immunoblotting using commercial and in-house antibodies, as well as individual and pooled patients' serum. PV isoforms were purified or recombinantly expressed before immunological analyses, including human mast cell degranulation assay., Results: Of the tissues analyzed, PV was most abundant in heated crocodile preparation, triggering an SPT of ≥3 mm in 8 of 12 (67%) fish-allergic patients. Seventy percent (31 of 44) of fish PV-sensitized patients demonstrated IgE-binding to crocodile PV. Crocodile β-PV was the major IgE-binding protein but 20-fold less abundant than α-PV. Cellular reactivity was demonstrated for β-PV and epitopes predicted, explaining frequent IgE-cross-binding of β-PVs. Both PV isoforms are now registered as the first reptile allergens with the WHO/IUIS (β-PV as Cro p 1 and α-PV as Cro p 2)., Conclusion: Fish-allergic individuals may be at risk of an allergy to crocodile and should seek specialist advice before consuming crocodilian meat., (© 2022 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)