bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and testing of mosaic enterovirus vaccine to prevent hand, foot and mouth disease
Authors: Greening Gage , McLennan Rebecca , Geanes Eric , Khanal Santosh , Rangaraj Suryabalan , Bradley Todd
Published: November 2024

Enterovirus A (EV-A) has been responsible for recent outbreaks of hand-foot-mouth disease (HFMD); however, there is no vaccine or effective antiviral treatment. The goal of our project is to develop broad vaccines targeting the diverse EV-A serotype viruses that cause HFMD. We used the EV-A viral capsid protein 1 (VP1) as the vaccine antigenic target, because of its genetic diversity across EV-A serotypes, and prior work that showed VP1 has linear neutralizing antibody epitopes. We computationally designed VP1 proteins to create mosaic antigens that optimize B and T cell epitopes among diverse EV-A viral sequences. We identified that a hexavalent mosaic vaccine cocktail had the highest EV-A sequence coverage. We then immunized mice in three groups with recombinant VP1 proteins in adjuvant; Group 1 was given the EV-A Consensus VP1 (Consensus), Group 2 was given the EV-A strain EVA-71 VP1 protein (EVA-71, strain specific) and Group 3 was given our newly designed hexavalent vaccine (EV-A Consensus + 5 mosaic VP1). We measured the antibody binding levels to 9 EV-A VP1 antigens after immunization and found that the EV-A hexavalent vaccine resulted in improved antibody binding breadth during in vivo vaccination. Our results demonstrate the feasibility of using polyvalent VP1 proteins to increase the breath of antibody epitopes among EV-A serotypes. Our approach has the potential to treat and block EV-A infection and serve as a model for responding to other emerging viral diseases.
Swine T cell responses to influenza A virus following live attenuated influenza virus or replicon particle vaccine
Authors: Wymore Brand Meghan , Kunzler Souza Carine , Arruda Bailey , Baker Amy
Published: November 2024

Influenza A virus (IAV) is a significant economic concern in the swine industry. Live attenuated influenza virus vaccines (LAIV) in swine are not available commercially but experimentally shown to induce mucosal cellular immunity. Non-adjuvanted hemagglutinin (HA) replicon particle (HA-RP) vaccines induce robust HA antibody, but little is reported about induction of T cell responses compared to LAIV. This study compared HA-RP and LAIV induction of T cell responses. Pigs were vaccinated with experimental LAIV or HA-RP, challenged with heterologous IAV, and necropsied at 5 or 21 days post infection. Virus titration was performed on nasal swabs and bronchoalveolar lavage fluid (BALF). T cells isolated from blood, lung, lymph node, and BALF were stimulated ex vivo with IAV and evaluated for cytokine production and proliferation. HA-RP-vaccinated pigs had lower macroscopic lesion scores but similar virus titers in nasal swabs and BALF to non-vaccine challenge (NV/CH) pigs. LAIV-vaccinated pigs had similar macroscopic lesion scores compared to NV/CH pigs but minimal virus titers. Both vaccines induced T cell production of IFNγ and TNFα and T cell proliferation after IAV stimulation, though LAIV responded at greater magnitude. In conclusion, both LAIV and HA-RP vaccines induced T cell responses and variable protection from heterologous IAV challenge. Understanding vaccine induction of cellular immunity as a correlate of protection will aid in improved swine IAV vaccine strategies.
Natural intraepithelial lymphocytes are critical intestinal defense against necrotic enteritis in chickens
Authors: Nazmi Ali , Majeed Shuja , Hamad Shaimaa , Shah Bikas , Bielke Lisa
Published: November 2024

In chickens, the subsets of intraepithelial lymphocytes (IEL) and their responses to enteric diseases remain unclear. Therefore, our study aimed to elucidate the roles of IEL populations in necrotic enteritis (NE) in chickens. At 14 days of age, 63 SPF chicks were randomly divided into 3 groups: Control (sham challenge), Eimeria maxima (EM) challenge, and Clostridium Perfringens (CP) challenge. Birds in the EM and CP groups were orally infected with EM at day 14 of age, and while CP birds received additional oral infection with CP bacteria at days 18 and 19 of age. At 20 days of age (1 day post CP infection; dpi), and 27 days of age (7 dpi), 7 birds per group were euthanized, and jejunum was harvested for gross lesion scores, IEL isolation, and gene expression. Birds exhibited subclinical NE based on lesion scores, and CP-infected birds showed lower BWG and shorter colon length. The Most changes in the IEL populations were observed at 1 dpi. The CP group showed substantial increases in the total number of natural IEL subsets, including TCRαβ+CD4-CD8-, TCRαβ+CD8αα+, TCRγδ+, TCRneg and iCD8α IEL. By 7 dpi, only the number of TCRαβ+CD4-CD8- and TCRαβ+CD8αα+ IEL maintain their increase in the CP group. The CP group had significant higher expression of IL-1β and IFN-γ and osteopontin genes at 1 dpi. These findings suggest that natural IEL play a critical role in the host response during subclinical NE, potentially conferring protection against CP infection.
A conserved TRAF binding motif within human 41BB enhances canine CD8+ CAR T cell expansion and cytolysis
Authors: Goodman Emma , Mason Nicola , Payne Aimee
Published: November 2024

Anti-CD19 chimeric antigen receptor T cells (CART) have transformed cancer therapy by inducing durable remissions of B cell cancers, although incomplete responses are common, highlighting a need for improved therapy. Immune competent dogs develop B cell lymphomas with similar pathophysiology as humans, offering a compelling opportunity for CART preclinical assessment. In a first-in-canine trial, anti-CD20 CART with canine 41BB and CD3ζ (caBBζ) domains exerted selective pressure on B cell lymphomas but did not persist or induce remission. We hypothesize canine CART signaling defects impair cytolytic activity and persistence. To optimize CAR design, we incorporated canine CD28 and CD3ζ (ca28ζ) or human (hu) BBζ and evaluated CART function and immunophenotype, using caBBζ as a reference control. In both an in vitro rechallenge and canine leukemia xenograft model, huBBζ CART elicited greater cytolysis and CD8 T cell outgrowth than caBBζ, and ca28ζ CART did not persist. Mutagenesis studies indicate T235 in the conserved PxQxT TRAF binding motif is required for CD8 outgrowth in huBBζ CART. Dogs and other mammals express A235, but introduction of A235T is not sufficient to confer CD8 outgrowth in caBBζ CART. Ongoing studies are profiling pathways downstream of ca/hu41BB that drive cytolytic activity and CD8 outgrowth. These studies reveal fundamental differences in T cell biology between humans and other mammals that hold promise for enabling clinical efficacy of canine CART.
Ultralong CDR3 cattlebody use biased to switched immunoglobulin isotypes in bovine immune tissues
Authors: Criscitiello Michael , Ott Jeannine , Sheppard Morgan , Whitley Casey , Ebert Nicholas
Published: November 2024

Alongside typical immunoglobulin (Ig), cattle express unique ultralong immunoglobulins (UL) that contain a CDR H3 comprised of a β-ribbon stalk and disulfide-linked knob that reaches over 70 amino acids in length. UL Ig exhibit potential "reach" to recessed pathogen epitopes and can provide broadly neutralizing antibodies to elusive antigens. This study explores the relative amounts of UL Ig in pre-switch isotypes (IgM and IgD) versus post-switch isotypes (IgG, IgA and IgE). Rearranged immunoglobulin heavy chain transcripts from primary and secondary lymphoid tissues of three steer were assessed with primers specific for the variable segments used in ultralong and canonical rearrangements as well as specific subisotype constant regions. Relative expression suggests biased selection for UL Ig in germinal centers and use in mucosal tissues of the ruminant gastrointestinal tract. Despite the explosion of studies exploring the immunogenetic diversification and binding possibilities of the UL Ig knob "picobody", our understanding of the use of the role of these antibodies in the Bovid immune system has been much slower. With a more complete understanding of tissue-specific expression patterns and isotype-specific immune responses using these exceptional paratopes, we'll be better poised to exploit them for improved bovine and human health.
Comparing visio-spatial intelligence in amateur rugby and netball players using hand-eye coordination tests
Authors: Millard Lourens , Breukelman Gerrit J. , Mathe Nonkululeko
Published: November 2024

Background: Research investigating the differences in visio-spatial skills (VSS) between athletes and non-athletes, as well as variations across sports, presents conflicting findings.Aim: The objective of this study was to determine if there exist significant differences in visio-spatial intelligence (VSI) skills between rugby players and netball players, and whether such disparities are present when comparing both groups to non-athletes.Setting: All participants, including the control group (non-athletes), rugby players and netball players, were recruited from the Zululand region of South Africa’s KwaZulu-Natal province, specifically from all premier league rugby and netball teams in the area.Methods: Participants underwent an optometric assessment, followed by an evaluation of VSS using six established tests: The Hart Near Far Rock, saccadic eye movement, evasion, accumulator, flash memory and ball wall toss tests.Results: The results revealed that rugby players significantly outperformed netball players in speed of recognition, peripheral awareness and hand-eye coordination (P = 0.000). Moreover, both rugby players and netball players performed significantly better than non-athletes in five of the six tests (P = 0.000), with the exception being the visual memory test (P = 0.809).Conclusion: This discrepancy in performance suggests that certain VSS are superior in athletes compared to non-athletes, highlighting potential implications for theories of vision, test selection and the development of sport-specific VSS testing batteries. Furthermore, the use of a hand-eye coordination-specific VSS test battery effectively differentiated between different sports.Contribution: The identified pattern was not consistent across all VSS tests, indicating that further research should explore the training methods employed by both sports, as these factors may contribute to the observed differences.
A Quasi-Experimental Study to Evaluate the Effectiveness of Hot Water Footbath Therapy on Quality of Sleep among Cancer Patients
Authors: Kumar Virendra , Rawat Alok , Charan Gopal Singh
Published: November 2024

Background:

Sleep disruptions are common among cancer patients, adversely affecting their quality of life and treatment outcomes. Warm foot baths have emerged as a potential intervention to improve sleep quality in this population, offering a noninvasive and holistic approach.

Materials and Methods:

A quasi-experimental study was conducted on 200 cancer patients in Rajasthan, India, with 100 participants in experimental and control groups. The hot water footbath intervention was administered to the experimental group, while the control group received standard care. Data were collected using demographic pro forma and the Groningen Sleep Quality Scale.

Results:

Baseline comparison revealed similar sleep quality levels between groups, but postintervention analysis showed significant differences. The experimental group exhibited higher proportions of disturbed and poor sleep, indicating a nuanced response to footbath intervention. However, the experimental group demonstrated a significantly higher mean sleep quality score (9.85 ± 2.47) compared to controls (8.97 ± 2.44). Statistical analysis confirmed the effectiveness of footbath therapy in improving sleep quality among cancer patients.

Conclusion:

Hot water footbath therapy effectively improved sleep quality among cancer patients despite varied responses within the experimental group. Integrating footbath therapy into cancer care regimens is recommended to alleviate sleep disturbances and enhance overall well-being during chemotherapy. Further research should explore additional nonpharmacological interventions to alleviate the challenges faced by cancer patients, aiming to optimize their quality of life.
Postpartum Pubic Diastasis with Significant Widening: A Rare Case Series
Authors: Prabhat Vinay , Trivedi Kiran , Prasad Verma Dipak Kumar Prakash , Topno Rohit
Published: November 2024

Postpartum pubic symphysis diastasis is a relatively rare entity. It is usually associated with cephalopelvic disproportion, macrosomia, multiparity, precipitate labor, difficult labor, difficult forceps delivery, any other pelvic bone pathologies, and underlying connective tissue disorders. Management is typically conservative in most cases, but surgical intervention is sometimes required in cases where pubic symphysis is >4 cm and not responding to conservative management. Case with more than 4 cm of pubic diastasis is usually associated with disruption of the symphyseal ligament, sacroiliac joint capsule, and ligaments. Surgical management promotes early ambulation with good functional recovery and decreases the chances of symphyseal sclerosis, functional disability, and chronic pain. Four female patients with postpartum pubic diastasis of more than 7 cm with an age ranging from 20 to 30 years underwent open reduction and internal fixation using plates and screws. In all four cases, the patient got early ambulation and full functional recovery without any pain, discomfort, and disability at 3 months of follow up. Although conservative management has been advocated for postpartum pubic diastasis typically, surgical intervention should be sought for significant pubic diastasis (more than 4 cm) to promote early full functional recovery and avoid chronic pain, functional disability, and symphyseal sclerosis.
Efficacy of Nebulized Dexmedetomidine and Lignocaine Inhalation versus Lignocaine Alone as Premedication for Flexible Fiber-optic Bronchoscopy under Sedation: A Randomized Comparative Study
Authors: Priyadarshini Anjali , Hembrom Boniface , Lakra Ladhu , Kumar Tushar
Published: November 2024

Introduction:

Airway management is an integral part of general anesthesia, allowing ventilation and oxygenation and working as a mode for delivering anesthetic gases. Awake fiber-optic-guided intubation is an essential component of airway management in difficult cases. We aim to study the benefits of nebulized dexmedetomidine with lignocaine over lignocaine alone for anesthetizing the airway for flexible fiber-optic bronchoscopy.

Materials and Methods:

In the study, after written informed consent, 50 patients were randomly allocated into two equal groups of 25 each. The intervention group received dexmedetomidine with lignocaine nebulization, while the control group received lignocaine nebulization alone. Baseline pulse rate, blood pressure, and, at regular intervals, cough, sedation, and pain scores were recorded along with the patient satisfaction score. Parametric data were analyzed by the Student’s t-test, while nonparametric data were analyzed by the Wilcoxon Mann–Whitney U test.

Results:

Out of a total of 54 patients, 4 patients did not give consent to participate in the study. The demographic profile was comparable in both groups. The pulse rate was comparable in both groups throughout the procedure; however, 10 min after the procedure, the pulse rate in the lignocaine group was (mean ± standard deviation) 114.2 ± 11.52, while in the intervention group, it was 87.32 ± 7.24 with a P = 0.027. The mean blood pressure was comparable throughout the procedure. The cough score yielded a Z-score of −5.12 and a P < 0.00001 favoring the dexmedetomidine group. Similarly, Richmond agitation-sedation score and Visual Analog Scale (VAS) also favored the intervention group, with P < 0.00054 and P < 0.00001 in RASS and VAS, respectively. Patient satisfaction score analysis found a Z-score of −5.29 and a P < 0.00001.

Conclusion:

The overall results favored dexmedetomidine with lignocaine nebulization over lignocaine alone for anesthetizing airways for flexible fiber-optic bronchoscopy.
Prevalence and Association of Components of Metabolic Syndrome and Uric Acid among Commercial Drivers in South-West Nigeria
Authors: Ajayi David D. , Raimi Taiwo H. , Dada Samuel A.
Published: November 2024

Introduction:

Metabolic syndrome (MetS) is a complex cluster of metabolic abnormalities characterized by central obesity, dyslipidemia, hypertension, and impaired glucose metabolism. Emerging evidence suggests a potential link between uric acid levels and MetS, and commercial drivers are exposed to unique occupational hazards that may predispose them to MetS and hyperuricemia.

Objectives:

The objective of this study was to determine the prevalence of MetS and its relationship with serum uric acid among commercial drivers in Ado-Ekiti, Nigeria.

Materials and Methods:

A cross-sectional study was conducted among commercial drivers in Ado-Ekiti. Relevant information was obtained with a questionnaire, and anthropometry and blood pressure were measured. Fasting plasma glucose and lipid profiles were determined by the standard protocol. MetS was determined with the harmonized criteria. Bivariate correlation and Chi-square were used to determine the relationship between serum uric acid and MetS and its components.

Results:

There were 106 participants with a median age (interquartile range) of 50 (11) years, with no difference between those with or without MetS. More than 70% of the participants drank alcohol and 75 (70.8%) participants had hyperuricemia. There was no significant correlation between serum uric acid and components of MetS. The prevalence of MetS among all the participants was 21.7% (23/106), with no difference among men with normal uric acid (25.8%) and those with elevated uric acid (20.0%), P = 0.509. Similarly, there was no statistical difference in the prevalence of the components of MetS between the two groups.

Conclusions:

The prevalence of MetS among the commercial drivers was high, with no difference among men with or without hyperuricemia. Given the importance of this group of people, a system-level public health approach should be adopted to promote a healthy lifestyle to save the lives of the populace.
Associations of Ureaplasma urealyticum infection with male infertility and intrauterine insemination outcomes
Authors: Wan Yang-Yang , Shi Xiao-Yun , Liu Wen-Jing , Bai Shun , Chen Xin , Li Si-Yao , Jiang Xiao-Hua , Wu Li-Min , Zhang Xian-Sheng , Hua Juan
Published: November 2024

Ureaplasma urealyticum (UU) is one of the most commonly occurring pathogens associated with genital tract infections in infertile males, but the impact of seminal UU infection in semen on intrauterine insemination (IUI) outcomes is poorly understood. We collected data from 245 infertile couples who underwent IUI at The First Affiliated Hospital of USTC (Hefei, China) between January 2021 and January 2023. The subjects were classified into two groups according to their UU infection status: the UU-positive group and the UU-negative group. We compared semen parameters, pregnancy outcomes, and neonatal birth outcomes to investigate the impact of UU infection on IUI outcomes. There were no significantly statistical differences in various semen parameters, including semen volume, sperm concentration, total and progressive motility, sperm morphology, leukocyte count, the presence of anti-sperm antibody, and sperm DNA fragmentation index (DFI), between the UU-positive and UU-negative groups of male infertile patients (all P > 0.05). However, the high DNA stainability (HDS) status of sperm differed between the UU-positive and UU-negative groups, suggesting that seminal UU infection may affect sperm nuclear maturation (P = 0.04). Additionally, there were no significant differences in pregnancy or neonatal birth outcomes between the two groups (all P > 0.05). These results suggest that IUI remains a viable and cost-effective option for infertile couples with UU infection who are facing infertility issues.
Lacrimal Gland Inflammation as the First Manifestation of Adult-onset Still’s Disease
Authors: Alhumud Atheer Mohammed , Alakel Raghad Mohammed , Alkhayyal Mashael A. , Althaqib Rawan N. , Alsulaiman Hamad M.
Published: November 2024

Adult-onset Still’s disease (AOSD) is a systemic idiopathic autoinflammatory disorder with rare ocular involvement. Few cases in the literature reported lacrimal gland inflammation as a manifestation of AOSD. Here, we present a case of a 38-year-old man who presented with an isolated unilateral lacrimal gland inflammation, few months later, he developed fever and arthritis and was investigated, diagnosed, and treated by rheumatology as AOSD. Resolution of lacrimal gland enlargement was achieved while on prednisolone and methotrexate. To the best of our knowledge, this is the first case to present with lacrimal gland inflammation as a first manifestation of AOSD.
Potential Impact of Online Self-Help Groups on Knowledge, Attitudes, and Quality of Life on Patients with Rheumatoid Arthritis Study, in Saudi Arabia 2023/2024
Authors: Alkhdairi Ahmad Abdulaziz , Alsugair Mashael Mohammed , Alrashdi Mousa Naser , Alrasheedi Sami Moteq , Alzweihari Ali Mohammed , Alharbi Mariyyah Muqbil , Alqubays Mayyaz Mohammed , Aljemeeli Feras Abdulrahman
Published: November 2024

Background:

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetrical inflammation of the joints and reduced quality of life (QoL). Limited research exists on how online self-help groups contribute to knowledge acquisition and enhancement.

Aims:

This study aims to fill this knowledge gap and estimate the impact of these groups on knowledge and QoL in RA patients.

Subjects and Methods:

An observational cross-sectional study was conducted in WhatsApp and Telegram online groups in Saudi Arabia from September 1, 2023, to April 2024. The target population is the RA patients participating in online supervised self-help groups. A nonconvenient sampling technique is used to collect the data, and SPSS software is used to analyze the results.

Results:

97.9% of participants were female, while only 2.1% of males participated in this research. 43.2% of participants were between the ages of 31 and 45 years. 36.9% of participants suffered from other rheumatoid or immune disease. All participants joined WhatsApp, Telegram, or both to learn about RA. Overall, most of the participants had satisfactory knowledge of RA. Their perceptions of joining the groups regarding RA were also clear and helpful.

Conclusions:

Findings indicate a notable understanding of RA via WhatsApp/Telegram, with improved QoL, yet revealing room for growth, mainly through targeted public education campaigns across diverse media platforms. Emphasizing inclusive online support networks could enhance RA management and improve the QoL of affected individuals in Saudi Arabia.
Factors Associated with Acute Respiratory Infection among Children Under 5 Years in India: Results from 2019 to 2021 National Family Health Survey
Authors: Thakkar Nandan , George Paul E. , Alam Prima , Yasobant Sandul , Saxena Deepak , Shah Jay
Published: November 2024

Introduction:

Acute respiratory infections (ARIs) remain the leading global cause of death in children under-five. Targeted initiatives are needed to address healthcare inequities and reduce under-five mortality, particularly in disproportionately impacted low- and middle- income countries. To inform initiatives and identify high-risk groups, this study explored regional risk factors for ARIs among Indian children.

Material and Methods:

Our retrospective, observational study utilized India’s National Family Health Survey (NFHS-5). Bivariate and multivariable models were employed to investigate associations between respiratory infections and explanatory variables, including environmental factors, child characteristics, maternal characteristics, enabling factors, and household characteristics.

Results:

Of the 201,133 children under-five included in our sample, 2.85% [2.78-2.92%] experienced a recent respiratory infection. In multivariate analysis, children from northern and central regions had the highest odds of infection, while those from the southern region had the lowest. Healthcare accessibility, maternal smoking, caste, age (child), and birthweight were among additional variables associated with infections. Our study revealed significant regional differences in prevalence of acute respiratory infection symptoms. Notably, inability to access healthcare increased a child’s risk of infection. Several states in southern India, which typically had lower ARI symptom rates, have adopted initiatives to strengthen public health infrastructure, including the WHO’s Integrated Management of Neonatal and Childhood Illnesses program. Such initiatives could serve as models for broader health improvement efforts across regions. Furthermore, observed variability in disease burden suggests that with detailed and deliberate implementation of programs, advancements in under-five mortality due to ARI can be achieved.
“Even though Doctor has Advised to Practice Foot Care I have not Practiced Soaking Feet in Lukewarm Water so Far” Self-care Practices, Enablers, and Barriers: A Mixed Methods Study among Individuals with Diabetes from a Rural Area of South India
Authors: Nirgude Abhay S. , Revathi TM , Navya Nagendra , Naik Poonam R.
Published: November 2024

Background:

Self-efficacy is the ability by which a person confronts problems in day-to-day life with goal- centered attitude. The clinician plays a vital role in promoting self-care though a series of social, cultural and economic factors also contribute positively towards it. This study was conducted to assess the self-care practices among diabetic individuals aged 30 years and above and to understand its enablers and barriers.

Materials and Methods:

Explanatory mixed method study was conducted from August 2018 to October2020. Quantitative assessment was done wherein a questionnaire was administered to 297 study participants enrolled by simple random sampling followed by in-depth interviews by purposive sampling as qualitative component. Multivariate logistic regression analysis was used to study the relationship of independent variables with various domains of self- care practice. P value <0.05 was considered as statistically significant.

Results:

Study found educational status, occupation and religion had a statistically significant association with self-care practices. Regular physical activity, good dietary practices and family support were a few enablers, whereas lack of awareness, time constraints, co-morbidities and environmental factors were some of the barriers to self-care practice.

Conclusions:

In the present study, self-care practice in terms of diet and physical activity were found to be good whereas blood sugar level monitoring and foot care practices were poor.
Parietal Cell Antibodies in Type 1 Diabetes Mellitus and Its Implications for Iron Deficiency: A Tertiary Centre Experience from North India
Authors: Bhat Khurshid A. , Verma Sonali , Bhatia Eesh , Bhatia Vijayalakshmi , Sudhanshu Siddhnath
Published: November 2024

Introduction:

Parietal cell antibody (PCA)-mediated auto-immune gastritis is known to increase the risk of iron-deficiency and pernicious anaemia in adults with type 1 diabetes mellitus. However, in children and young adults with type 1 diabetes, these data are scarce. We aimed to study the prevalence of parietal cell antibodies (PCAs) and its clinical associations in people with type 1 diabetes with onset below 30 years.

Methods:

In a cross-sectional study, 224 children and young adults with type 1 diabetes and 171 healthy controls were enrolled. We measured haemoglobin, serum ferritin, vitamin B12, PCA, thyroid peroxidase, and anti-tissue transglutaminase antibodies in all patients. Mann–Whitney U test for continuous data and Chi square test for categorical data were used. Linear regression analysis was performed with haemoglobin as a dependent variable.

Results:

The prevalence of PCA was significantly higher in patients than in controls (22% vs 10.2%; P = 0.002). Patients with PCA had a higher frequency of anaemia (60% vs 30%, P < 0.001), lower haemoglobin [7.3 (1.6) vs 7.8 (1.1) mmol/L; P = 0.002], and lower serum ferritin [46.9 (70.8) pmol/L vs 66.0 (105.3) pmol/L; P = 0.04], as compared to those without PCA. On multivariate analysis, haemoglobin was associated with PCA (β = -0.174, P = 0.005) and serum ferritin (β =0.247, P < 0.001).

Conclusion:

Presence of PCA was an independent risk factor for iron deficiency and anaemia in children and young adults with type 1 diabetes.
Cutaneous manifestations and sequelae of Chikungunya fever: a single centre experience
Authors: Chatterjee Rupak , Ampi Padi , Rongong Sabina Liangon Joanna , Mukherjee Shatavisa , Pramanik Netai , Podder Indrashis
Published: November 2024

Background: Chikungunya fever is a common viral illness in the tropical and subtropical areas. Various cutaneous manifestations can develop during the acute phase and post-febrile convalescent phase. Objective: To determine the frequency and types of cutaneous manifestations associated with chikungunya fever in acute and post-febrile phase. Methods: We conducted a prospective, observational study including 20 patients with laboratory-confirmed chikungunya fever. All the patients were followed up for 1 year to detect any cutaneous sequelae. Results: Pruritic maculopapular rash was the most common cutaneous manifestation during the acute febrile phase, noted in 60% of the patients. The rash usually appeared within 1–3 days of fever onset and spread in cephalo-caudal direction. Cutaneous hyperpigmentation was the most common dermatologic sequelae in the post-febrile period, occurring in 3 (15%) patients. In all patients, pigmentation appeared 3–4 weeks after resolution of fever, and started on the nose, gradually spreading to the forehead. The pigmentation improved significantly with topical hydroquinone after 4 weeks. Other additional manifestations of chikungunya fever included joint pain and joint swelling. None of our patients presented with mucosal or systemic involvement. Conclusion: Maculopapular skin rash was the most common manifestation during acute febrile phase of chikungunya fever, while cutaneous hyperpigmentation was the most common dermatologic sequelae after resolution of fever.
A note on an effective characterization of covers with an application to higher rank representations
Authors: Aougab Tarik , Lahn Max , Loving Marissa , Miller Nicholas
Published: November 2024

In this note we prove an effective characterization of when two finite-degree covers of a connected, orientable surface of negative Euler characteristic are isomorphic in terms of which curves have simple elevations, weakening the hypotheses to consider curves with explicitly bounded self-intersection number. As an application we show that for sufficiently large 

N

, the set of unmarked traces associated to simple closed curves in a generically chosen representation to

\mathrm{SL}_{N}(\mathbb{R})

distinguishes between pairs of non-isomorphic covers.
Indefinite perturbations of an unbalanced growth eigenvalue problem
Authors: Bai Yunru , Papageorgiou Nikolaos S. , Zeng Shengda
Published: November 2024

We consider indefinite perturbations of a double-phase eigenvalue problem. The perturbation is sublinear or superlinear, and it is in general sign-changing. Using the Nehari manifold, we prove the existence of two constant sign solutions for both cases (sublinear and superlinear), when the parameter

\lambda\in (0,\hat{\lambda}^{\alpha}_{1})

with

\hat{\lambda}^{\alpha}_{1}>0

being the principal eigenvalue of Dirichlet weighted

p

-Laplace operator

-\Delta^{\alpha}_{p}

.
Prognostic prediction models for postoperative patients with stage I to III colorectal cancer based on machine learning
Authors: Ji Xiao-Lin , Xu Shuo , Li Xiao-Yu , Xu Jin-Huan , Han Rong-Shuang , Guo Ying-Jie , Duan Li-Ping , Tian Zi-Bin
Published: November 2024

BACKGROUND

Colorectal cancer (CRC) is characterized by high heterogeneity, aggressiveness, and high morbidity and mortality rates. With machine learning (ML) algorithms, patient, tumor, and treatment features can be used to develop and validate models for predicting survival. In addition, important variables can be screened and different applications can be provided that could serve as vital references when making clinical decisions and potentially improving patient outcomes in clinical settings.

AIM

To construct prognostic prediction models and screen important variables for patients with stage I to III CRC.

METHODS

More than 1000 postoperative CRC patients were grouped according to survival time (with cutoff values of 3 years and 5 years) and assigned to training and testing cohorts (7:3). For each 3-category survival time, predictions were made by 4 ML algorithms (all-variable and important variable-only datasets), each of which was validated via 5-fold cross-validation and bootstrap validation. Important variables were screened with multivariable regression methods. Model performance was evaluated and compared before and after variable screening with the area under the curve (AUC). SHapley Additive exPlanations (SHAP) further demonstrated the impact of important variables on model decision-making. Nomograms were constructed for practical model application.

RESULTS

Our ML models performed well; the model performance before and after important parameter identification was consistent, and variable screening was effective. The highest pre- and postscreening model AUCs 95% confidence intervals in the testing set were 0.87 (0.81-0.92) and 0.89 (0.84-0.93) for overall survival, 0.75 (0.69-0.82) and 0.73 (0.64-0.81) for disease-free survival, 0.95 (0.88-1.00) and 0.88 (0.75-0.97) for recurrence-free survival, and 0.76 (0.47-0.95) and 0.80 (0.53-0.94) for distant metastasis-free survival. Repeated cross-validation and bootstrap validation were performed in both the training and testing datasets. The SHAP values of the important variables were consistent with the clinicopathological characteristics of patients with tumors. The nomograms were created.

CONCLUSION

We constructed a comprehensive, high-accuracy, important variable-based ML architecture for predicting the 3-category survival times. This architecture could serve as a vital reference for managing CRC patients.
Nomogram model based on γ-glutamyl transferase to albumin ratio predicts survival in hepatocellular carcinoma patients with transarterial chemoembolization treatment
Authors: Wu Zhen-Ying , Li Han , Chen Jia-Li , Su Ke , Weng Mei-Ling , Han Yun-Wei
Published: November 2024

BACKGROUND

The development of tumor is closely linked to inflammation. Therefore, targeting molecules involved in inflammation may be effective in predicting cancer prognosis. Transarterial chemoembolization (TACE) holds significant therapeutic significance in addressing hepatocellular carcinoma (HCC). At present, no studies have evaluated the predictive value of γ-glutamyl transferase to albumin ratio (GAR) on the prognosis of HCC undergoing TACE.

AIM

To explore the potential prognostic significance of the GAR in individuals undergoing TACE for HCC.

METHODS

A total of 1231 patients from seven hospitals in China were randomized into a training cohort (n = 862) and a validation cohort (n = 369). To establish independent prognostic factors for overall survival (OS), we utilized multivariate and univariate Cox regression models. The best cut-off value of the GAR was determined with the X-tile software, with OS as the basis. Validations were performed using dual therapy cohort and triple therapy cohort.

RESULTS

X-tile software revealed a GAR threshold of 4.75 as optimal. Both pre- and post-propensity score matching analyses demonstrated that the median OS in the low-GAR group (< 4.75) was notably longer compared to the high-GAR group (≥ 4.75), showing results of 26.9 vs 9.8 months (P < 0.001) initially, and 18.1 vs 11.3 months (P < 0.001) after match. Furthermore, multivariate analysis identified GAR ≥ 4.75 as an independent prognostic factor (P < 0.001). The receiver operating characteristic curves for the nomogram showed area under receiver operating characteristic curves of 0.741, 0.747, and 0.708 for predicting 1-, 2-, and 3-year survival, respectively. Consistent findings were reiterated in the two cohorts involving TACE in combination with targeted therapy and TACE in combination with targeted therapy and immunotherapy. Calibration curve and decision curve analyses substantiated the model’s relatively robust predictive capabilities.

CONCLUSION

Our study validates the effective prognostic capacity of the GAR-based nomogram for HCC patients undergoing TACE or TACE in combination with systemic therapy.
Matrine promotes colorectal cancer apoptosis by downregulating shank-associated RH domain interactor expression
Authors: Zhou Yuan-Chen , Wang Qian-Qian , Zhou Ge-Yu-Jia , Yin Teng-Fei , Zhao Dong-Yan , Sun Xi-Zhen , Tan Chang , Zhou Lei , Yao Shu-Kun
Published: November 2024

BACKGROUND

The 5-year survival rate of patients with colorectal cancer (CRC) in China is only 56.9%, highlighting the need for new therapeutic drugs. Previous studies have shown that matrine exhibits antitumor effects by inducing apoptosis. However, the mechanism by which matrine regulates antiapoptotic proteins in CRC remains unclear.

AIM

To identify apoptotic proteins from proteomics and investigate the role of matrine in impeding CRC apoptosis by regulating these proteins.

METHODS

Tumor and adjacent normal tissues were collected from 52 patients with CRC who underwent surgery between January and December 2021. Data-independent acquisition quantitative proteomic analysis was performed to identify differentially expressed apoptotic proteins. The selected apoptotic proteins were identified through their association with tumor-node-metastasis (TNM) stage and prognosis, then confirmed by immunohistochemical (IHC) staining in validation cohort. In vitro , the role of matrine or apoptotic proteins on cancer cells were analyzed.

RESULTS

Compared to normal tissues, 88 anti-apoptotic proteins from proteomic results were selected. Among them, Shank-associated RH domain interactor (SHARPIN) was identified because of its relationship with TNM stage and overall survival in TCGA database. In the IHC-confirmed cohort, SHARPIN was highly expressed in CRC tissues and localized in the cytoplasm. Higher SHARPIN expression was associated with TNM stage, carbohydrate antigen 153 levels, and gross type compared to low expression. SHARPIN knockdown promoted apoptosis, significantly upregulated the expression of Bcl-2 associated agonist of cell death, Bcl-2 associated X protein, caspase 3, and caspase 8, and downregulated B-cell lymphoma-2 (P < 0.05). Importantly, matrine treatment promoted apoptosis and reversed the proliferation, invasion, and migration of CRC cells by repressing SHARPIN.

CONCLUSION

SHARPIN was identified as an upregulated anti-apoptotic protein in CRC, and matrine exhibited anticancer effects by downregulating its expression. Thus, matrine appears to be a promising drug for CRC.
Pain Management in Cancer Patients: The Effectiveness of Digital Game-based Interventions: A Rapid Literature Review
Authors: Savareh Behrouz Alizadeh , Karandish Zahra , Farhoudi Fardis , Bashiri Azadeh
Published: November 2024

Objectives: Pain is a common side effect of cancer that negatively impacts biopsychosocial well-being and quality of life. There has been increasing interest in using digital game interventions for managing pain in cancer patients. The present study aimed to consolidate and summarize knowledge regarding the role of games in reducing pain among cancer patients and enhancing their overall quality of life.Methods: We reviewed studies published between 2000 and April 8, 2023, from databases such as PubMed, Scopus, and Web of Science. The focus was on determining the impact of health games on pain management in cancer patients.Results: An initial search identified 2,544 studies, which were narrowed down to 10 relevant articles after removing duplicates and assessing quality. These studies examined the use of mobile and computer games across various types of cancer, including both pediatric and adult cases. The findings indicate that digital games, particularly those utilizing virtual reality technologies, can diminish pain and anxiety while enhancing treatment outcomes. Overall, the application of these technologies has the potential to improve cancer treatment.Conclusions: Digital game interventions empower cancer patients by fostering effective communication and patient-centered approaches, which enhance perceptions, outcomes, and overall well-being. These games provide real-time feedback and facilitate interaction with healthcare professionals, which promotes self-management and boosts patient motivation and adherence to treatment protocols. As personalized educational platforms, they increase engagement through educational resources and symptom tracking, while also encouraging physical activity. Furthermore, they act as distraction tools during painful procedures, presenting new research opportunities in pain management and enhancing overall quality of life.
Mapping Drug Terms via Integration of a Retrieval-Augmented Generation Algorithm with a Large Language Model
Authors: Kimura Eizen , Kawakami Yukinobu , Inoue Shingo , Okajima Ai
Published: November 2024

Objectives: This study evaluated the efficacy of integrating a retrieval-augmented generation (RAG) model and a large language model (LLM) to improve the accuracy of drug name mapping across international vocabularies.Methods: Drug ingredient names were translated into English using the Japanese Accepted Names for Pharmaceuticals. Drug concepts were extracted from the standard vocabulary of OHDSI, and the accuracy of mappings between translated terms and RxNorm was assessed by vector similarity, using the BioBERT-generated embedded vectors as the baseline. Subsequently, we developed LLMs with RAG that distinguished the final candidates from the baseline. We assessed the efficacy of the LLM with RAG in candidate selection by comparing it with conventional methods based on vector similarity.Results: The evaluation metrics demonstrated the superior performance of the combined LLM + RAG over traditional vector similarity methods. Notably, the hit rates of the Mixtral 8x7b and GPT-3.5 models exceeded 90%, significantly outperforming the baseline rate of 64% across stratified groups of PO drugs, injections, and all interventions. Furthermore, the r-precision metric, which measures the alignment between model judgment and human evaluation, revealed a notable improvement in LLM performance, ranging from 41% to 50% compared to the baseline of 23%.Conclusions: Integrating an RAG and an LLM outperformed conventional string comparison and embedding vector similarity techniques, offering a more refined approach to global drug information mapping.
Elastomer: Silicone Rubber (MQ/VMQ/PVMQ) Extreme Low-Temperature Resistant 35 – 45 Durometer Type ‘A’
Authors:   AMS CE Elastomers Committee
Published: November 2024

This specification covers a silicone (MQ/VMQ/PVMQ) elastomer that can be used to manufacture product in the form of sheet, strip, tubing, extrusions, and molded shapes. This specification should not be designated for use in molded O-rings and molded O-ring cord, molded rings, compression seals, molded-in-place gaskets, and plate seals for aeronautical and aerospace applications.
Impact of Customer Service Management on the Survival of Micro, Small and Medium Scale Enterprise (MSMEs) in Asaba, Delta State, Nigeria
Authors: Ifeanyi Tochukwu , Onwuka Offor , Emaviwe Elo
Published: November 2024

Currently, many micro, small and medium-scale enterprises suffers from a crumbling infrastructure that acts as a significant drag on operational efficiency and, consequently, customer service delivery, hence, the study examined the impact of customer service management on the survival of micro, small, and medium scale enterprises (MSME) in Asaba, Delta State, Nigeria. The study adopted Descriptive Survey Research Design. Data were collected using structured questionnaire. Hypotheses were tested using Correlation Analysis and OLS Regression with the aid of Statistical Packages for Social Sciences (version 25). Findings revealed that there is a revealed significant impact of customer service management on the survival of micro, small, and medium scale enterprises (MSME) in Asaba, Delta State, Nigeria. The findings concluded that the research offers a foundation for future studies and interventions aimed at optimizing business performance and underscores the critical importance of customer-related factors in the success of MSMEs. The study recommended that MSMEs should invest in comprehensive customer satisfaction programs, also, streamline their customer support systems to ensure that issues are resolved quickly and effectively during the first contact, lastly, develop robust retention strategies.
Strategic Management and Governance Practices in Local Government Authorities of Tanzania: A Review of Resource-Based – Theory
Authors: Pandisha Haghai , Kombe Wilbard , Kayunze Kim
Published: November 2024

This study examines the effectiveness of the Resource-Based View (RBV) framework in improving accountability and transparency in service delivery and resource allocation in Local Government Authorities (LGAs) in Tanzania. Despite adopting Strategic Management Practices (SMPs), LGAs face challenges in promoting sustainable development and meeting community needs. A qualitative research design was employed, using Mufindi District Council as a case study, and data was collected through semi-structured interviews, focus group discussions, and document reviews. The study found that the implementation of SMPs has not improved accountability and transparency in service delivery and resource allocation, with staff lacking a clear understanding of the SMP implementation process, which was non-transparent and complicated. Resource allocation was also poorly budgeted, hindering the council's ability to achieve its goals. The study recommends comprehensive management reforms, including staff capacity building and integrating modern management practices into SMP implementation, to enhance staff and leader accountability and improve the overall governance of LGAs, ultimately promoting sustainable development and community well-being. The study's findings highlight the need for improved accountability and transparency in service delivery and resource allocation in LGAs, and emphasize the importance of effective management practices in achieving sustainable development goals.